nach oben

Cancer and Metastasis Reviews

Erschienen in:

09.01.2023 | Non-Thematic Review

Mesenchymal stromal cell senescence in haematological malignancies

verfasst von: Natalya Plakhova, Vasilios Panagopoulos, Kate Vandyke, Andrew C. W. Zannettino, Krzysztof M. Mrozik

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1/2023

Einloggen, um Zugang zu erhalten

Abstract

Acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM) are age-related haematological malignancies with defined precursor states termed myelodysplastic syndrome (MDS), monoclonal B-cell lymphocytosis (MBL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. While the progression from asymptomatic precursor states to malignancy is widely considered to be mediated by the accumulation of genetic mutations in neoplastic haematopoietic cell clones, recent studies suggest that intrinsic genetic changes, alone, may be insufficient to drive the progression to overt malignancy. Notably, studies suggest that extrinsic, microenvironmental changes in the bone marrow (BM) may also promote the transition from these precursor states to active disease. There is now enhanced focus on extrinsic, age-related changes in the BM microenvironment that accompany the development of AML, CLL, and MM. One of the most prominent changes associated with ageing is the accumulation of senescent mesenchymal stromal cells within tissues and organs. In comparison with proliferating cells, senescent cells display an altered profile of secreted factors (secretome), termed the senescence-associated-secretory phenotype (SASP), comprising proteases, inflammatory cytokines, and growth factors that may render the local microenvironment favourable for cancer growth. It is well established that BM mesenchymal stromal cells (BM-MSCs) are key regulators of haematopoietic stem cell maintenance and fate determination. Moreover, there is emerging evidence that BM-MSC senescence may contribute to age-related haematopoietic decline and cancer development. This review explores the association between BM-MSC senescence and the development of haematological malignancies, and the functional role of senescent BM-MSCs in the development of these cancers.

Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., Kandoth, C., Fulton, R. S., McLellan, M. D., Dooling, D. J., Wallis, J. W., Chen, K., Harris, C. C., Schmidt, H. K., Kalicki-Veizer, J. M., Lu, C., et al. (2012). The origin and evolution of mutations in acute myeloid leukemia. Cell, 150(2), 264–278. https://doi.org/10.1016/j.cell.2012.06.023CrossRefPubMedPubMedCentral

Steensma, D. P., Bejar, R., Jaiswal, S., Lindsley, R. C., Sekeres, M. A., Hasserjian, R. P., & Ebert, B. L. (2015). Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood, 126(1), 9–16. https://doi.org/10.1182/blood-2015-03-631747CrossRefPubMedPubMedCentral

Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P., Mar, B. G., Lindsley, R. C., Mermel, C., Burtt, N., Chavez, A., Higgins, J. M., Moltchanov, V., Kinnunen, L., Koistinen, H., Ladenvall, C., Getz, G., Correa, A., Gabriel, S., Kathiresan, S., Stringham, H., et al. (2014). Clonal hematopoiesis with somatic mutations is a common, age-related condition associated with adverse outcomes. Blood, 124(21), 840. https://doi.org/10.1056/NEJMoa1408617CrossRef

Young, A. L., Challen, G. A., Birmann, B. M., & Druley, T. E. (2016). Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults. Nature Communucations, 7, 12484. https://doi.org/10.1038/ncomms12484CrossRef

Veiga, C. B., Lawrence, E. M., Murphy, A. J., Herold, M. J., & Dragoljevic, D. (2021). Myelodysplasia syndrome, clonal hematopoiesis and cardiovascular disease. Cancers, 13(8), 1968. https://doi.org/10.3390/cancers13081968

Strati, P., & Shanafelt, T. D. (2015). Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: Diagnosis, natural history, and risk stratification. Blood, 126(4), 454–462. https://doi.org/10.1182/blood-2015-02-585059CrossRefPubMedPubMedCentral

Kyle, R. A., Larson, D. R., Therneau, T. M., Dispenzieri, A., Kumar, S., Cerhan, J. R., & Rajkumar, S. V. (2018). Long-term follow-up of monoclonal gammopathy of undetermined significance. New England Journal of Medicine, 378(3), 241–249. https://doi.org/10.1056/NEJMoa1709974CrossRefPubMed

Genovese, G., Kahler, A. K., Handsaker, R. E., Lindberg, J., Rose, S. A., Bakhoum, S. F., Chambert, K., Mick, E., Neale, B. M., Fromer, M., Purcell, S. M., Svantesson, O., Landen, M., Hoglund, M., Lehmann, S., Gabriel, S. B., Moran, J. L., Lander, E. S., Sullivan, P. F., Sklar, P., et al. (2014). Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. New England Journal of Medicine, 371(26), 2477–2487. https://doi.org/10.1056/NEJMoa1409405CrossRefPubMed

Ma, X., Does, M., Raza, A., & Mayne, S. T. (2007). Myelodysplastic syndromes: Incidence and survival in the United States. Cancer, 109(8), 1536–1542. https://doi.org/10.1002/cncr.22570CrossRefPubMed

10.

Shim, Y. K., Middleton, D. C., Caporaso, N. E., Rachel, J. M., Landgren, O., Abbasi, F., Raveche, E. S., Rawstron, A. C., Orfao, A., Marti, G. E., & Vogt, R. F. (2010). Prevalence of monoclonal B-cell lymphocytosis: a systematic review. Cytometry. Part B: Clinical Cytometry, 78. https://doi.org/10.1002/cyto.b.20538

11.

Kyle, R. A., Therneau, T. M., Rajkumar, S. V., Larson, D. R., Plevak, M. F., Offord, J. R., Dispenzieri, A., Katzmann, J. A., & Melton, L. J., 3rd. (2006). Prevalence of monoclonal gammopathy of undetermined significance. New England Journal of Medicine, 354(13), 1362–1369. https://doi.org/10.1056/NEJMoa054494CrossRefPubMed

12.

Costa, L. J., Brill, I. K., Omel, J., Godby, K., Kumar, S. K., & Brown, E. E. (2017). Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States. Blood Advances, 1(4), 282–287. https://doi.org/10.1182/bloodadvances.2016002493CrossRefPubMedPubMedCentral

13.

Hallek, M., Shanafelt, T. D., & Eichhorst, B. (2018). Chronic lymphocytic leukaemia. Lancet, 391(10129), 1524–1537. https://doi.org/10.1016/S0140-6736(18)30422-7CrossRefPubMed

14.

Oran, B., & Weisdorf, D. J. (2012). Survival for older patients with acute myeloid leukemia: A population-based study. Haematologica, 97(12), 1916–1924. https://doi.org/10.3324/haematol.2012.066100CrossRefPubMedPubMedCentral

15.

Rozhok, A. I., Salstrom, J. L., & DeGregori, J. (2014). Stochastic modeling indicates that aging and somatic evolution in the hematopoetic system are driven by non-cell-autonomous processes. Aging, 6(12), 1033–1048. https://doi.org/10.18632/aging.100707CrossRefPubMedPubMedCentral

16.

Dutta, A. K., Fink, J. L., Grady, J. P., Morgan, G. J., Mullighan, C. G., To, L. B., Hewett, D. R., & Zannettino, A. C. W. (2019). Subclonal evolution in disease progression from MGUS/SMM to multiple myeloma is characterised by clonal stability. Leukemia, 33(2), 457–468. https://doi.org/10.1038/s41375-018-0206-xCrossRefPubMed

17.

Das, R., Strowig, T., Verma, R., Koduru, S., Hafemann, A., Hopf, S., Kocoglu, M. H., Borsotti, C., Zhang, L., Branagan, A., Eynon, E., Manz, M. G., Flavell, R. A., & Dhodapkar, M. V. (2016). Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice. Nature Medicine, 22(11), 1351–1357. https://doi.org/10.1038/nm.4202CrossRefPubMedPubMedCentral

18.

Medyouf, H., Mossner, M., Jann, J.-C., Nolte, F., Raffel, S., Herrmann, C., Lier, A., Eisen, C., Nowak, V., Zens, B., Müdder, K., Klein, C., Obländer, J., Fey, S., Vogler, J., Fabarius, A., Riedl, E., Roehl, H., Kohlmann, A., Staller, M., et al. (2014). Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell, 14(6), 824–837. https://doi.org/10.1016/j.stem.2014.02.014CrossRefPubMed

19.

Balderman, S. R., Li, A. J., Hoffman, C. M., Frisch, B. J., Goodman, A. N., LaMere, M. W., Georger, M. A., Evans, A. G., Liesveld, J. L., Becker, M. W., & Calvi, L. M. (2016). Targeting of the bone marrow microenvironment improves outcome in a murine model of myelodysplastic syndrome. Blood, 127(5), 616–625. https://doi.org/10.1182/blood-2015-06-653113CrossRefPubMedPubMedCentral

20.

Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., Saltness, A., & R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., Khazaie, K., Miller, J. D., & van Deursen, J. M. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530, 184. https://doi.org/10.1038/nature16932CrossRefPubMedPubMedCentral

21.

Jeon, O. H., Kim, C., Laberge, R. M., Demaria, M., Rathod, S., Vasserot, A. P., Chung, J. W., Kim, D. H., Poon, Y., David, N., Baker, D. J., van Deursen, J. M., Campisi, J., & Elisseeff, J. H. (2017). Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nature Medicine, 23(6), 775–781. https://doi.org/10.1038/nm.4324CrossRefPubMedPubMedCentral

22.

Farr, J. N., Fraser, D. G., Wang, H., Jaehn, K., Ogrodnik, M. B., Weivoda, M. M., Drake, M. T., Tchkonia, T., LeBrasseur, N. K., Kirkland, J. L., Bonewald, L. F., Pignolo, R. J., Monroe, D. G., & Khosla, S. (2016). Identification of Senescent Cells in the Bone Microenvironment. Journal of Bone and Mineral Research, 31(11), 1920–1929. https://doi.org/10.1002/jbmr.2892CrossRefPubMed

23.

Lawrenson, K., Grun, B., Benjamin, E., Jacobs, I. J., Dafou, D., & Gayther, S. A. (2010). Senescent fibroblasts promote neoplastic transformation of partially transformed ovarian epithelial cells in a three-dimensional model of early stage ovarian cancer. Neoplasia, 12(4), 317–325. https://doi.org/10.1593/neo.91948CrossRefPubMedPubMedCentral

24.

Krtolica, A., Parrinello, S., Lockett, S., Desprez, P. Y., & Campisi, J. (2001). Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging. Proceedings of the National Academy of Sciences of the United States of America, 98(21), 12072–12077. https://doi.org/10.1073/pnas.211053698CrossRefPubMedPubMedCentral

25.

Coppé, J. P., Patil, C. K., Rodier, F., Krtolica, A., Beauséjour, C. M., Parrinello, S., Hodgson, J. G., Chin, K., Desprez, P. Y., & Campisi, J. (2010). A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE, 5(2), e9188. https://doi.org/10.1371/journal.pone.0009188CrossRefPubMedPubMedCentral

26.

Di, G. H., Liu, Y., Lu, Y., Liu, J., Wu, C., & Duan, H. F. (2014). IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells. PLoS ONE, 9(11), e113572. https://doi.org/10.1371/journal.pone.0113572CrossRefPubMedPubMedCentral

27.

Laberge, R. M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., Limbad, C., Demaria, M., Li, P., Hubbard, G. B., Ikeno, Y., Javors, M., Desprez, P. Y., Benz, C. C., Kapahi, P., Nelson, P. S., et al. (2015). MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nature Cell Biology, 17(8), 1049–1061. https://doi.org/10.1038/ncb3195CrossRefPubMedPubMedCentral

28.

Liu, D., & Hornsby, P. J. (2007). Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Research, 67(7), 3117–3126. https://doi.org/10.1158/0008-5472.Can-06-3452CrossRefPubMed

29.

Luo, X., Fu, Y., Loza, A. J., Murali, B., Leahy, K. M., Ruhland, M. K., Gang, M., Su, X., Zamani, A., Shi, Y., Lavine, K. J., Ornitz, D. M., Weilbaecher, K. N., Long, F., Novack, D. V., Faccio, R., Longmore, G. D., & Stewart, S. A. (2016). Stromal-initiated changes in the bone promote metastatic niche development. Cell Reports, 14(1), 82–92. https://doi.org/10.1016/j.celrep.2015.12.016CrossRefPubMed

30.

Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315–317. https://doi.org/10.1080/14653240600855905CrossRefPubMed

31.

Goulard, M., Dosquet, C., & Bonnet, D. (2018). Role of the microenvironment in myeloid malignancies. Cellular and Molecular Life Sciences, 75(8), 1377–1391. https://doi.org/10.1007/s00018-017-2725-4CrossRefPubMed

32.

Mendelson, A., & Frenette, P. S. (2014). Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nature Medicine, 20(8), 833–846. https://doi.org/10.1038/nm.3647CrossRefPubMedPubMedCentral

33.

Wei, Q., & Frenette, P. S. (2018). Niches for Hematopoietic Stem Cells and Their Progeny. Immunity, 48(4), 632–648. https://doi.org/10.1016/j.immuni.2018.03.024CrossRefPubMedPubMedCentral

34.

Mitroulis, I., Kalafati, L., Bornhauser, M., Hajishengallis, G., & Chavakis, T. (2020). Regulation of the bone marrow niche by inflammation. Frontiers in Immunology, 11, 1540. https://doi.org/10.3389/fimmu.2020.01540CrossRefPubMedPubMedCentral

35.

Passegue, E., Wagers, A. J., Giuriato, S., Anderson, W. C., & Weissman, I. L. (2005). Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. Journal of Experimental Medicine, 202(11), 1599–1611. https://doi.org/10.1084/jem.20050967CrossRefPubMedPubMedCentral

36.

Kunisaki, Y., Bruns, I., Scheiermann, C., Ahmed, J., Pinho, S., Zhang, D., Mizoguchi, T., Wei, Q., Lucas, D., Ito, K., Mar, J. C., Bergman, A., & Frenette, P. S. (2013). Arteriolar niches maintain haematopoietic stem cell quiescence. Nature, 502(7473), 637–643. https://doi.org/10.1038/nature12612CrossRefPubMedPubMedCentral

37.

Acar, M., Kocherlakota, K. S., Murphy, M. M., Peyer, J. G., Oguro, H., Inra, C. N., Jaiyeola, C., Zhao, Z., Luby-Phelps, K., & Morrison, S. J. (2015). Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature, 526(7571), 126–130. https://doi.org/10.1038/nature15250CrossRefPubMedPubMedCentral

38.

Sugiyama, T., Kohara, H., Noda, M., & Nagasawa, T. (2006). Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity, 25(6), 977–988. https://doi.org/10.1016/j.immuni.2006.10.016CrossRefPubMed

39.

Omatsu, Y., Sugiyama, T., Kohara, H., Kondoh, G., Fujii, N., Kohno, K., & Nagasawa, T. (2010). The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity, 33(3), 387–399. https://doi.org/10.1016/j.immuni.2010.08.017CrossRefPubMed

40.

Mendez-Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., Macarthur, B. D., Lira, S. A., Scadden, D. T., Ma’ayan, A., Enikolopov, G. N., & Frenette, P. S. (2010). Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 466(7308), 829–834. https://doi.org/10.1038/nature09262CrossRefPubMedPubMedCentral

41.

Zhou, B. O., Yue, R., Murphy, M. M., Peyer, J. G., & Morrison, S. J. (2014). Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell, 15(2), 154–168. https://doi.org/10.1016/j.stem.2014.06.008CrossRefPubMedPubMedCentral

42.

Lawson, M. A., McDonald, M. M., Kovacic, N., Hua Khoo, W., Terry, R. L., Down, J., Kaplan, W., Paton-Hough, J., Fellows, C., Pettitt, J. A., Neil Dear, T., Van Valckenborgh, E., Baldock, P. A., Rogers, M. J., Eaton, C. L., Vanderkerken, K., Pettit, A. R., Quinn, J. M., Zannettino, A. C., Phan, T. G., et al. (2015). Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche. Nature Communications, 6, 8983. https://doi.org/10.1038/ncomms9983CrossRefPubMed

43.

Agarwal, P., & Bhatia, R. (2015). Influence of bone marrow microenvironment on leukemic stem cells: Breaking up an intimate relationship. Advances in Cancer Research, 127, 227–252. https://doi.org/10.1016/bs.acr.2015.04.007CrossRefPubMed

44.

Agarwal, P., Isringhausen, S., Li, H., Paterson, A. J., He, J., Gomariz, A., Nagasawa, T., Nombela-Arrieta, C., & Bhatia, R. (2019). Mesenchymal niche-specific expression of Cxcl12 controls quiescence of treatment-resistant leukemia stem cells. Cell Stem Cell, 24(5), 769–784 e766. https://doi.org/10.1016/j.stem.2019.02.018

45.

Kode, A., Manavalan, J. S., Mosialou, I., Bhagat, G., Rathinam, C. V., Luo, N., Khiabanian, H., Lee, A., Murty, V. V., Friedman, R., Brum, A., Park, D., Galili, N., Mukherjee, S., Teruya-Feldstein, J., Raza, A., Rabadan, R., Berman, E., & Kousteni, S. (2014). Leukaemogenesis induced by an activating beta-catenin mutation in osteoblasts. Nature, 506(7487), 240–244. https://doi.org/10.1038/nature12883CrossRefPubMedPubMedCentral

46.

Krevvata, M., Silva, B. C., Manavalan, J. S., Galan-Diez, M., Kode, A., Matthews, B. G., Park, D., Zhang, C. A., Galili, N., Nickolas, T. L., Dempster, D. W., Dougall, W., Teruya-Feldstein, J., Economides, A. N., Kalajzic, I., Raza, A., Berman, E., Mukherjee, S., Bhagat, G., & Kousteni, S. (2014). Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood, 124(18), 2834–2846. https://doi.org/10.1182/blood-2013-07-517219CrossRefPubMedPubMedCentral

47.

Bowers, M., Zhang, B., Ho, Y., Agarwal, P., Chen, C. C., & Bhatia, R. (2015). Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development. Blood, 125(17), 2678–2688. https://doi.org/10.1182/blood-2014-06-582924CrossRefPubMedPubMedCentral

48.

Raaijmakers, M. H., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., & Scadden, D. T. (2010). Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature, 464(7290), 852–857. https://doi.org/10.1038/nature08851CrossRefPubMedPubMedCentral

49.

Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015). Cellular senescence in aging and age-related disease: From mechanisms to therapy. Nature Medicine, 21(12), 1424–1435. https://doi.org/10.1038/nm.4000CrossRefPubMedPubMedCentral

50.

Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., &, et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences of the United States of America, 92(20), 9363–9367. https://doi.org/10.1073/pnas.92.20.9363CrossRefPubMedPubMedCentral

51.

Mammoto, T., Torisawa, Y. S., Muyleart, M., Hendee, K., Anugwom, C., Gutterman, D., & Mammoto, A. (2019). Effects of age-dependent changes in cell size on endothelial cell proliferation and senescence through YAP1. Aging, 11(17), 7051–7069. https://doi.org/10.18632/aging.102236

52.

Kumari, R., & Jat, P. (2021). Mechanisms of cellular senescence: Cell cycle arrest and senescence associated secretory phenotype. Frontiers in Cell and Developmental Biology, 9, 645593. https://doi.org/10.3389/fcell.2021.645593CrossRefPubMedPubMedCentral

53.

Mirzayans, R., Andrais, B., Hansen, G., & Murray, D. (2012). Role of p16(INK4A) in Replicative Senescence and DNA Damage-induced premature senescence in p53-deficient human cells. Biochemistry Research International, 2012, 951574. https://doi.org/10.1155/2012/951574CrossRefPubMedPubMedCentral

54.

Petrova, N. V., Velichko, A. K., Razin, S. V., & Kantidze, O. L. (2016). Small molecule compounds that induce cellular senescence. Aging Cell, 15(6), 999–1017. https://doi.org/10.1111/acel.12518CrossRefPubMedPubMedCentral

55.

Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004). Ink4a/Arf expression is a biomarker of aging. Journal of Clinical Investigation, 114(9), 1299–1307. https://doi.org/10.1172/jci22475CrossRefPubMedPubMedCentral

56.

Roninson, I. B. (2003). Tumor cell senescence in cancer treatment. Cancer Research, 63(11), 2705–2715.PubMed

57.

van Deursen, J. M. (2014). The role of senescent cells in ageing. Nature, 509(7501), 439–446. https://doi.org/10.1038/nature13193CrossRefPubMedPubMedCentral

58.

Wang, E. (1995). Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. Cancer Research, 55(11), 2284.PubMed

59.

Ray, D., & Yung, R. (2018). Immune senescence, epigenetics and autoimmunity. Clinical Immunology, 196, 59–63. https://doi.org/10.1016/j.clim.2018.04.002CrossRefPubMed

60.

Prata, L., Ovsyannikova, I. G., Tchkonia, T., & Kirkland, J. L. (2018). Senescent cell clearance by the immune system: Emerging therapeutic opportunities. Seminars in Immunology, 40, 101275. https://doi.org/10.1016/j.smim.2019.04.003CrossRefPubMed

61.

Coppe, J. P., Desprez, P. Y., Krtolica, A., & Campisi, J. (2010). The senescence-associated secretory phenotype: The dark side of tumor suppression. Annual Review of Pathology, 5, 99–118. https://doi.org/10.1146/annurev-pathol-121808-102144CrossRefPubMedPubMedCentral

62.

Freund, A., Orjalo, A. V., Desprez, P.-Y., & Campisi, J. (2010). Inflammatory networks during cellular senescence: Causes and consequences. Trends in Molecular Medicine, 16(5), 238–246. https://doi.org/10.1016/j.molmed.2010.03.003CrossRefPubMedPubMedCentral

63.

Kale, A., Sharma, A., Stolzing, A., Desprez, P.-Y., & Campisi, J. (2020). Role of immune cells in the removal of deleterious senescent cells. Immunity & Ageing, 17(1), 16. https://doi.org/10.1186/s12979-020-00187-9CrossRef

64.

Brennan, F. M., Maini, R. N., & Feldmann, M. (1995). Cytokine expression in chronic inflammatory disease. British Medical Bulletin, 51(2), 368–384. https://doi.org/10.1093/oxfordjournals.bmb.a072967CrossRefPubMed

65.

Caruso, C., Lio, D., Cavallone, L., & Franceschi, C. (2004). Aging, longevity, inflammation, and cancer. Annals of the New York Academy of Sciences, 1028, 1–13. https://doi.org/10.1196/annals.1322.001CrossRefPubMed

66.

Brod, S. A. (2000). Unregulated inflammation shortens human functional longevity. Inflammation Research, 49(11), 561–570. https://doi.org/10.1007/s000110050632CrossRefPubMed

67.

Buscarlet, M., Provost, S., Zada, Y. F., Barhdadi, A., Bourgoin, V., Lepine, G., Mollica, L., Szuber, N., Dube, M. P., & Busque, L. (2017). DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood, 130(6), 753–762. https://doi.org/10.1182/blood-2017-04-777029CrossRefPubMed

68.

Beerman, I., Bhattacharya, D., Zandi, S., Sigvardsson, M., Weissman, I. L., Bryder, D., & Rossi, D. J. (2010). Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proceedings of the National Academy of Sciences of the United States of America, 107(12), 5465–5470. https://doi.org/10.1073/pnas.1000834107CrossRefPubMedPubMedCentral

69.

Linton, P. J., & Dorshkind, K. (2004). Age-related changes in lymphocyte development and function. Nature Immunology, 5(2), 133–139. https://doi.org/10.1038/ni1033CrossRefPubMed

70.

Guralnik, J. M., Eisenstaedt, R. S., Ferrucci, L., Klein, H. G., & Woodman, R. C. (2004). Prevalence of anemia in persons 65 years and older in the United States: Evidence for a high rate of unexplained anemia. Blood, 104(8), 2263–2268. https://doi.org/10.1182/blood-2004-05-1812CrossRefPubMed

71.

Ogawa, T., Kitagawa, M., & Hirokawa, K. (2000). Age-related changes of human bone marrow: A histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages. Mechanisms of Ageing and Development, 117(1–3), 57–68. https://doi.org/10.1016/s0047-6374(00)00137-8CrossRefPubMed

72.

Bousounis, P., Bergo, V., & Trompouki, E. (2021). Inflammation, aging and hematopoiesis: a complex relationship. Cells, 10(6), 1386. https://doi.org/10.3390/cells10061386

73.

Ergen, A. V., Boles, N. C., & Goodell, M. A. (2012). Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood, 119(11), 2500–2509. https://doi.org/10.1182/blood-2011-11-391730CrossRefPubMedPubMedCentral

74.

Zhao, Y., Wu, D., Fei, C., Guo, J., Gu, S., Zhu, Y., Xu, F., Zhang, Z., Wu, L., Li, X., & Chang, C. (2015). Down-regulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome. Haematologica, 100(2), 194–204. https://doi.org/10.3324/haematol.2014.109769CrossRefPubMedPubMedCentral

75.

Guo, J., Zhao, Y., Fei, C., Zhao, S., Zheng, Q., Su, J., Wu, D., Li, X., & Chang, C. (2018). Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells. Cell Death & Disease, 9(5), 512. https://doi.org/10.1038/s41419-018-0545-6CrossRef

76.

Pang, W. W., Price, E. A., Sahoo, D., Beerman, I., Maloney, W. J., Rossi, D. J., Schrier, S. L., & Weissman, I. L. (2011). Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proceedings of the National Academy of Sciences of the United States of America, 108(50), 20012–20017. https://doi.org/10.1073/pnas.1116110108CrossRefPubMedPubMedCentral

77.

O’Hagan-Wong, K., Nadeau, S., Carrier-Leclerc, A., Apablaza, F., Hamdy, R., Shum-Tim, D., Rodier, F., & Colmegna, I. (2016). Increased IL-6 secretion by aged human mesenchymal stromal cells disrupts hematopoietic stem and progenitor cells’ homeostasis. Oncotarget, 7(12), 13285–13296. https://doi.org/10.18632/oncotarget.7690CrossRefPubMedPubMedCentral

78.

Adams, P. D., Jasper, H., & Rudolph, K. L. (2015). Aging-induced stem cell mutations as drivers for disease and cancer. Cell Stem Cell, 16, 601–612. https://doi.org/10.1016/j.stem.2015.05.002CrossRefPubMedPubMedCentral

79.

Tsai, K. K., Chuang, E. Y., Little, J. B., & Yuan, Z. M. (2005). Cellular mechanisms for low-dose ionizing radiation-induced perturbation of the breast tissue microenvironment. Cancer Research, 65(15), 6734–6744. https://doi.org/10.1158/0008-5472.CAN-05-0703CrossRefPubMed

80.

Bavik, C., Coleman, I., Dean, J. P., Knudsen, B., Plymate, S., & Nelson, P. S. (2006). The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. Cancer Research, 66(2), 794–802. https://doi.org/10.1158/0008-5472.CAN-05-1716CrossRefPubMed

81.

Takasugi, M., Okada, R., Takahashi, A., Virya Chen, D., Watanabe, S., & Hara, E. (2017). Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nature Communications, 8(1), 15729. https://doi.org/10.1038/ncomms15728CrossRefPubMedPubMedCentral

82.

Li, Y., Xu, X., Wang, L., Liu, G., Li, Y., Wu, X., Jing, Y., Li, H., & Wang, G. (2015). Senescent mesenchymal stem cells promote colorectal cancer cells growth via galectin-3 expression. Cell & Bioscience, 5, 21. https://doi.org/10.1186/s13578-015-0012-3CrossRef

83.

Capell, B. C., Drake, A. M., Zhu, J., Shah, P. P., Dou, Z., Dorsey, J., Simola, D. F., Donahue, G., Sammons, M., Rai, T. S., Natale, C., Ridky, T. W., Adams, P. D., & Berger, S. L. (2016). MLL1 is essential for the senescence-associated secretory phenotype. Genes and Development, 30(3), 321–336. https://doi.org/10.1101/gad.271882.115CrossRefPubMedPubMedCentral

84.

Coppe, J. P., Patil, C. K., Rodier, F., Sun, Y., Munoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P. Y., & Campisi, J. (2008). Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biology, 6(12), 2853–2868. https://doi.org/10.1371/journal.pbio.0060301CrossRefPubMed

85.

Krause, J. R. (2009). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues: An Overview. Critical Values, 2(2), 30–32. https://doi.org/10.1093/criticalvalues/2.2.30CrossRef

86.

Geyh, S., Oz, S., Cadeddu, R. P., Frobel, J., Bruckner, B., Kundgen, A., Fenk, R., Bruns, I., Zilkens, C., Hermsen, D., Gattermann, N., Kobbe, G., Germing, U., Lyko, F., Haas, R., & Schroeder, T. (2013). Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells. Leukemia, 27(9), 1841–1851. https://doi.org/10.1038/leu.2013.193CrossRefPubMed

87.

Poloni, A., Maurizi, G., Mattiucci, D., Amatori, S., Fogliardi, B., Costantini, B., Mariani, M., Mancini, S., Olivieri, A., Fanelli, M., & Leoni, P. (2014). Overexpression of CDKN2B (p15INK4B) and altered global DNA methylation status in mesenchymal stem cells of high-risk myelodysplastic syndromes. Leukemia, 28(11), 2241–2244. https://doi.org/10.1038/leu.2014.197CrossRefPubMed

88.

Lopez-Villar, O., Garcia, J. L., Sanchez-Guijo, F. M., Robledo, C., Villaron, E. M., Hernández-Campo, P., Lopez-Holgado, N., Diez-Campelo, M., Barbado, M. V., Perez-Simon, J. A., Hernández-Rivas, J. M., San-Miguel, J. F., & del Cañizo, M. C. (2009). Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q− syndrome. Leukemia, 23, 664. https://doi.org/10.1038/leu.2008.361CrossRefPubMed

89.

Aanei, C. M., Flandrin, P., Eloae, F. Z., Carasevici, E., Guyotat, D., Wattel, E., & Campos, L. (2012). Intrinsic growth deficiencies of mesenchymal stromal cells in myelodysplastic syndromes. Stem Cells and Development, 21(10), 1604–1615. https://doi.org/10.1089/scd.2011.0390CrossRefPubMed

90.

Fei, C., Zhao, Y., Guo, J., Gu, S., Li, X., & Chang, C. (2014). Senescence of bone marrow mesenchymal stromal cells is accompanied by activation of p53/p21 pathway in myelodysplastic syndromes. European Journal of Haematology, 93(6), 476–486. https://doi.org/10.1111/ejh.12385CrossRefPubMed

91.

Kornblau, S. M., Ruvolo, P. P., Wang, R. Y., Battula, V. L., Shpall, E. J., Ruvolo, V. R., McQueen, T., Qui, Y., Zeng, Z., Pierce, S., Jacamo, R., Yoo, S. Y., Le, P. M., Sun, J., Hail, N., Jr., Konopleva, M., & Andreeff, M. (2018). Distinct protein signatures of acute myeloid leukemia bone marrow-derived stromal cells are prognostic for patient survival. Haematologica, 103(5), 810–821. https://doi.org/10.3324/haematol.2017.172429CrossRefPubMedPubMedCentral

92.

Chandran, P., Le, Y., Li, Y., Sabloff, M., Mehic, J., Rosu-Myles, M., & Allan, D. S. (2015). Mesenchymal stromal cells from patients with acute myeloid leukemia have altered capacity to expand differentiated hematopoietic progenitors. Leukemia Research, 39(4), 486–493. https://doi.org/10.1016/j.leukres.2015.01.013CrossRefPubMed

93.

Choi, H., Kim, Y., Kang, D., Kwon, A., Kim, J., Min Kim, J., Park, S. S., Kim, Y. J., Min, C. K., & Kim, M. (2020). Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma. Cell Proliferation, 53(5), e12819. https://doi.org/10.1111/cpr.12819CrossRefPubMedPubMedCentral

94.

Geyh, S., Rodríguez-Paredes, M., Jäger, P., Khandanpour, C., Cadeddu, R. P., Gutekunst, J., Wilk, C. M., Fenk, R., Zilkens, C., Hermsen, D., Germing, U., Kobbe, G., Lyko, F., Haas, R., & Schroeder, T. (2016). Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia. Leukemia, 30(3), 683–691. https://doi.org/10.1038/leu.2015.325CrossRefPubMed

95.

Falconi, G., Fabiani, E., Fianchi, L., Criscuolo, M., Raffaelli, C. S., Bellesi, S., Hohaus, S., Voso, M. T., D'Alo, F., & Leone, G. (2016). Impairment of PI3K/AKT and WNT/beta-catenin pathways in bone marrow mesenchymal stem cells isolated from patients with myelodysplastic syndromes. Experimental Hematology, 44(1), 75–83 e71–74, https://doi.org/10.1016/j.exphem.2015.10.005

96.

Poon, Z., Dighe, N., Venkatesan, S. S., Cheung, A. M. S., Fan, X., Bari, S., Hota, M., Ghosh, S., & Hwang, W. Y. K. (2019). Bone marrow MSCs in MDS: Contribution towards dysfunctional hematopoiesis and potential targets for disease response to hypomethylating therapy. Leukemia, 33(6), 1487–1500. https://doi.org/10.1038/s41375-018-0310-yCrossRefPubMed

97.

Boada, M., Echarte, L., Guillermo, C., Diaz, L., Touriño, C., & Grille, S. (2021). 5-Azacytidine restores interleukin 6-increased production in mesenchymal stromal cells from myelodysplastic patients. Hematology, Transfusion and Cell Therapy, 43(1), 35–42. https://doi.org/10.1016/j.htct.2019.12.0CrossRefPubMed

98.

Lopes, M. R., Pereira, J. K., de Melo Campos, P., Machado-Neto, J. A., Traina, F., Saad, S. T., & Favaro, P. (2017). De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes. Scientific Reports, 7, 40707. https://doi.org/10.1038/srep40707CrossRefPubMedPubMedCentral

99.

von der Heide, E. K., Neumann, M., Vosberg, S., James, A. R., Schroeder, M. P., Ortiz-Tanchez, J., Isaakidis, K., Schlee, C., Luther, M., Johrens, K., Anagnostopoulos, I., Mochmann, L. H., Nowak, D., Hofmann, W. K., Greif, P. A., & Baldus, C. D. (2017). Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients. Leukemia, 31(5), 1069–1078. https://doi.org/10.1038/leu.2016.324CrossRefPubMed

100.

Cheng, J., Li, Y., Liu, S., Jiang, Y., Ma, J., Wan, L., Li, Q., & Pang, T. (2019). CXCL8 derived from mesenchymal stromal cells supports survival and proliferation of acute myeloid leukemia cells through the PI3K/AKT pathway. The Federation of American Societies of Experimental Biology Journal, 33(4), 4755–4764. https://doi.org/10.1096/fj.201801931RCrossRef

101.

Pardanani, A., Finke, C., Lasho, T. L., Al-Kali, A., Begna, K. H., Hanson, C. A., & Tefferi, A. (2012). IPSS-independent prognostic value of plasma CXCL10, IL-7 and IL-6 levels in myelodysplastic syndromes. Leukemia, 26(4), 693–699. https://doi.org/10.1038/leu.2011.251CrossRefPubMed

102.

Shi, X., Zheng, Y., Xu, L., Cao, C., Dong, B., & Chen, X. (2019). The inflammatory cytokine profile of myelodysplastic syndromes: A meta-analysis. Medicine (Baltimore), 98(22), e15844. https://doi.org/10.1097/MD.0000000000015844CrossRefPubMed

103.

Desbourdes, L., Javary, J., Charbonnier, T., Ishac, N., Bourgeais, J., Iltis, A., Chomel, J. C., Turhan, A., Guilloton, F., Tarte, K., Demattei, M. V., Ducrocq, E., Rouleux-Bonnin, F., Gyan, E., Herault, O., & Domenech, J. (2017). Alteration analysis of bone marrow mesenchymal stromal cells from de novo acute myeloid leukemia patients at diagnosis. Stem Cells and Development, 26(10), 709–722. https://doi.org/10.1089/scd.2016.0295CrossRefPubMed

104.

Abdul-Aziz, A. M., Sun, Y., Hellmich, C., Marlein, C. R., Mistry, J., Forde, E., Piddock, R. E., Shafat, M. S., Morfakis, A., Mehta, T., Di Palma, F., Macaulay, I., Ingham, C. J., Haestier, A., Collins, A., Campisi, J., Bowles, K. M., & Rushworth, S. A. (2019). Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment. Blood, 133(5), 446–456. https://doi.org/10.1182/blood-2018-04-845420CrossRefPubMedPubMedCentral

105.

Su, Y. C., Li, S. C., Wu, Y. C., Wang, L. M., Chao, K. S., & Liao, H. F. (2013). Resveratrol downregulates interleukin-6-stimulated sonic hedgehog signaling in human acute myeloid leukemia. Evidence-Based Complementary and Alternative Medicine, 2013, 547430. https://doi.org/10.1155/2013/547430CrossRefPubMedPubMedCentral

106.

Saily, M., Koistinen, P., Zheng, A., & Savolainen, E. R. (1998). Signaling through interleukin-6 receptor supports blast cell proliferation in acute myeloblastic leukemia. European Journal of Haematology, 61(3), 190–196. https://doi.org/10.1111/j.1600-0609.1998.tb01083.xCrossRefPubMed

107.

Abdul-Aziz, A. M., Shafat, M. S., Mehta, T. K., Di Palma, F., Lawes, M. J., Rushworth, S. A., & Bowles, K. M. (2017). MIF-Induced Stromal PKCbeta/IL8 Is Essential in Human Acute Myeloid Leukemia. Cancer Research, 77(2), 303–311. https://doi.org/10.1158/0008-5472.CAN-16-1095CrossRefPubMed

108.

Hallek, M., Cheson, B. D., Catovsky, D., Caligaris-Cappio, F., Dighiero, G., Dohner, H., Hillmen, P., Keating, M. J., Montserrat, E., Rai, K. R., Kipps, T. J., & International Workshop on Chronic Lymphocytic, L. (2008). Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood, 111(12), 5446–5456. https://doi.org/10.1182/blood-2007-06-093906CrossRef

109.

Pontikoglou, C., Kastrinaki, M. C., Klaus, M., Kalpadakis, C., Katonis, P., Alpantaki, K., Pangalis, G. A., & Papadaki, H. A. (2013). Study of the quantitative, functional, cytogenetic, and immunoregulatory properties of bone marrow mesenchymal stem cells in patients with B-cell chronic lymphocytic leukemia. Stem Cells and Development, 22(9), 1329–1341. https://doi.org/10.1089/scd.2012.0255CrossRefPubMed

110.

Janel, A., Dubois-Galopin, F., Bourgne, C., Berger, J., Tarte, K., Boiret-Dupre, N., Boisgard, S., Verrelle, P., Dechelotte, P., Tournilhac, O., & Berger, M. G. (2014). The chronic lymphocytic leukemia clone disrupts the bone marrow microenvironment. Stem Cells and Development, 23(24), 2972–2982. https://doi.org/10.1089/scd.2014.0229CrossRefPubMed

111.

Kay, N. E., Shanafelt, T. D., Strege, A. K., Lee, Y. K., Bone, N. D., & Raza, A. (2007). Bone biopsy derived marrow stromal elements rescue chronic lymphocytic leukemia B-cells from spontaneous and drug induced cell death and facilitates an “angiogenic switch.” Leukemia Research, 31(7), 899–906. https://doi.org/10.1016/j.leukres.2006.11.024CrossRefPubMedPubMedCentral

112.

Fayad, L., Keating, M. J., Reuben, J. M., O’Brien, S., Lee, B. N., Lerner, S., & Kurzrock, R. (2001). Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: Correlation with phenotypic characteristics and outcome. Blood, 97(1), 256–263. https://doi.org/10.1182/blood.v97.1.256CrossRefPubMed

113.

Molica, S., Vitelli, G., Levato, D., Gandolfo, G. M., & Liso, V. (1999). Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia. British Journal of Haematology, 107(3), 605–610. https://doi.org/10.1046/j.1365-2141.1999.01752.xCrossRefPubMed

114.

Wierda, W. G., Johnson, M. M., Do, K. A., Manshouri, T., Dey, A., O’Brien, S., Giles, F. J., Kantarjian, H., Thomas, D., Faderl, S., Lerner, S., Keating, M., & Albitar, M. (2003). Plasma interleukin 8 level predicts for survival in chronic lymphocytic leukaemia. British Journal of Haematology, 120(3), 452–456. https://doi.org/10.1046/j.1365-2141.2003.04118.xCrossRefPubMed

115.

Yoon, J. Y., Lafarge, S., Dawe, D., Lakhi, S., Kumar, R., Morales, C., Marshall, A., Gibson, S. B., & Johnston, J. B. (2012). Association of interleukin-6 and interleukin-8 with poor prognosis in elderly patients with chronic lymphocytic leukemia. Leukemia and Lymphoma, 53(9), 1735–1742. https://doi.org/10.3109/10428194.2012.666662CrossRefPubMed

116.

Lai, R., O’Brien, S., Maushouri, T., Rogers, A., Kantarjian, H., Keating, M., & Albitar, M. (2002). Prognostic value of plasma interleukin-6 levels in patients with chronic lymphocytic leukemia. Cancer, 95(5), 1071–1075. https://doi.org/10.1002/cncr.10772CrossRefPubMed

117.

Ferrajoli, A., Keating, M. J., Manshouri, T., Giles, F. J., Dey, A., Estrov, Z., Koller, C. A., Kurzrock, R., Thomas, D. A., Faderl, S., Lerner, S., O’Brien, S., & Albitar, M. (2002). The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia. Blood, 100(4), 1215–1219. https://doi.org/10.1182/blood.V100.4.1215.h81602001215_1215_1219CrossRefPubMed

118.

Zhu, F., McCaw, L., Spaner, D. E., & Gorczynski, R. M. (2018). Targeting the IL-17/IL-6 axis can alter growth of chronic lymphocytic leukemia in vivo/in vitro. Leukemia Research, 66, 28–38. https://doi.org/10.1016/j.leukres.2018.01.006CrossRefPubMed

119.

Panayiotidis, P., Jones, D., Ganeshaguru, K., Foroni, L., & Hoffbrand, A. V. (1996). Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro. British Journal of Haematology, 92(1), 97–103. https://doi.org/10.1046/j.1365-2141.1996.00305.xCrossRefPubMed

120.

Trimarco, V., Ave, E., Facco, M., Chiodin, G., Frezzato, F., Martini, V., Gattazzo, C., Lessi, F., Giorgi, C. A., Visentin, A., Castelli, M., Severin, F., Zambello, R., Piazza, F., Semenzato, G., & Trentin, L. (2015). Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival. Oncotarget, 6(39), 42130–42149. https://doi.org/10.18632/oncotarget.6239CrossRefPubMedPubMedCentral

121.

Crompot, E., Van Damme, M., Pieters, K., Vermeersch, M., Perez-Morga, D., Mineur, P., Maerevoet, M., Meuleman, N., Bron, D., Lagneaux, L., & Stamatopoulos, B. (2017). Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications. Haematologica, 102(9), 1594–1604. https://doi.org/10.3324/haematol.2016.163337CrossRefPubMedPubMedCentral

122.

Gehrke, I., Gandhirajan, R. K., Poll-Wolbeck, S. J., Hallek, M., & Kreuzer, K. A. (2011). Bone marrow stromal cell-derived vascular endothelial growth factor (VEGF) rather than chronic lymphocytic leukemia (CLL) cell-derived VEGF is essential for the apoptotic resistance of cultured CLL cells. Molecular Medicine, 17(7–8), 619–627. https://doi.org/10.2119/molmed.2010.00210CrossRefPubMedPubMedCentral

123.

Lee, Y. K., Bone, N. D., Strege, A. K., Shanafelt, T. D., Jelinek, D. F., & Kay, N. E. (2004). VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG). B-cell chronic lymphocytic leukemia. Blood, 104(3), 788–794. https://doi.org/10.1182/blood-2003-08-2763CrossRefPubMed

124.

Paesler, J., Gehrke, I., Gandhirajan, R. K., Filipovich, A., Hertweck, M., Erdfelder, F., Uhrmacher, S., Poll-Wolbeck, S. J., Hallek, M., & Kreuzer, K. A. (2010). The vascular endothelial growth factor receptor tyrosine kinase inhibitors vatalanib and pazopanib potently induce apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Clinical Cancer Research, 16(13), 3390–3398. https://doi.org/10.1158/1078-0432.CCR-10-0232CrossRefPubMed

125.

Francia di Celle, P., Mariani, S., Riera, L., Stacchini, A., Reato, G., & Foa, R. (1996). Interleukin-8 induces the accumulation of B-cell chronic lymphocytic leukemia cells by prolonging survival in an autocrine fashion. Blood, 87(10), 4382–4389. https://doi.org/10.1182/blood.V87.10.4382.bloodjournal87104382CrossRefPubMed

126.

Blanco, G., Puiggros, A., Sherry, B., Nonell, L., Calvo, X., Puigdecanet, E., Chiu, P. Y., Kieso, Y., Ferrer, G., Palacios, F., Arnal, M., Rodriguez-Rivera, M., Gimeno, E., Abella, E., Rai, K. R., Abrisqueta, P., Bosch, F., Calon, A., Ferrer, A., Chiorazzi, N., et al. (2021). Chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia. Experimental Hematology, 95, 68–80. https://doi.org/10.1016/j.exphem.2020.12.007CrossRefPubMedPubMedCentral

127.

Aguilar-Santelises, M., Loftenius, A., Ljungh, C., Svenson, S. B., Andersson, B., Mellstedt, H., & Jondal, M. (1992). Serum levels of helper factors (IL-1α, IL-1β and IL-6), T-cell products (sCD4 and sCD8), sIL-2R and β2-microglobulin in patients with B-CLL and benign B lymphocytosis. Leukemia Research, 16(6–7), 607–613. https://doi.org/10.1016/0145-2126(92)90009-vCrossRefPubMed

128.

Rajkumar, S. V., Dimopoulos, M. A., Palumbo, A., Blade, J., Merlini, G., Mateos, M. V., Kumar, S., Hillengass, J., Kastritis, E., Richardson, P., Landgren, O., Paiva, B., Dispenzieri, A., Weiss, B., LeLeu, X., Zweegman, S., Lonial, S., Rosinol, L., Zamagni, E., Jagannath, S., et al. (2014). International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncology, 15(12), e538-548. https://doi.org/10.1016/S1470-2045(14)70442-5CrossRefPubMed

129.

Andre, T., Meuleman, N., Stamatopoulos, B., De Bruyn, C., Pieters, K., Bron, D., & Lagneaux, L. (2013). Evidences of early senescence in multiple myeloma bone marrow mesenchymal stromal cells. PLoS ONE, 8(3), e59756. https://doi.org/10.1371/journal.pone.0059756CrossRefPubMedPubMedCentral

130.

Garderet, L., Mazurier, C., Chapel, A., Ernou, I., Boutin, L., Holy, X., Gorin, N. C., Lopez, M., Doucet, C., & Lataillade, J. J. (2007). Mesenchymal stem cell abnormalities in patients with multiple myeloma. Leukemia Lymphoma, 48(10), 2032–2041. https://doi.org/10.1080/10428190701593644CrossRefPubMed

131.

Xu, S., Evans, H., Buckle, C., De Veirman, K., Hu, J., Xu, D., Menu, E., De Becker, A., Vande Broek, I., Leleu, X., Camp, B. V., Croucher, P., Vanderkerken, K., & Van Riet, I. (2012). Impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients is associated with a blockade in the deactivation of the Notch signaling pathway. Leukemia, 26(12), 2546–2549. https://doi.org/10.1038/leu.2012.126CrossRefPubMed

132.

Corre, J., Mahtouk, K., Attal, M., Gadelorge, M., Huynh, A., Fleury-Cappellesso, S., Danho, C., Laharrague, P., Klein, B., Reme, T., & Bourin, P. (2007). Bone marrow mesenchymal stem cells are abnormal in multiple myeloma. Leukemia, 21(5), 1079–1088. https://doi.org/10.1038/sj.leu.2404621CrossRefPubMedPubMedCentral

133.

Guo, J., Fei, C., Zhao, Y., Zhao, S., Zheng, Q., Su, J., Wu, D., Li, X., & Chang, C. (2017). Lenalidomide restores the osteogenic differentiation of bone marrow mesenchymal stem cells from multiple myeloma patients via deactivating Notch signaling pathway. Oncotarget, 8(33), 55405–55421. https://doi.org/10.18632/oncotarget.19265CrossRefPubMedPubMedCentral

134.

Mehdi, S. J., Johnson, S. K., Epstein, J., Zangari, M., Qu, P., Hoering, A., van Rhee, F., Schinke, C., Thanendrarajan, S., Barlogie, B., Davies, F. E., Morgan, G. J., & Yaccoby, S. (2019). Mesenchymal stem cells gene signature in high-risk myeloma bone marrow linked to suppression of distinct IGFBP2-expressing small adipocytes. British Journal of Haematology, 184(4), 578–593. https://doi.org/10.1111/bjh.15669CrossRefPubMed

135.

Berenstein, R., Blau, O., Nogai, A., Waechter, M., Slonova, E., Schmidt-Hieber, M., Kunitz, A., Pezzutto, A., Doerken, B., & Blau, I. W. (2015). Multiple myeloma cells alter the senescence phenotype of bone marrow mesenchymal stromal cells under participation of the DLK1-DIO3 genomic region. BMC Cancer, 15(1), 68. https://doi.org/10.1186/s12885-015-1078-3CrossRefPubMedPubMedCentral

136.

Fairfield, H., Costa, S., Falank, C., Farrell, M., Murphy, C. S., D’Amico, A., Driscoll, H., & Reagan, M. R. (2020). Multiple Myeloma Cells Alter Adipogenesis, Increase Senescence-Related and Inflammatory Gene Transcript Expression, and Alter Metabolism in Preadipocytes. Frontiers in Oncology, 10, 584683. https://doi.org/10.3389/fonc.2020.584683CrossRefPubMed

137.

Mahtouk, K., Moreaux, J., Hose, D., Reme, T., Meissner, T., Jourdan, M., Rossi, J. F., Pals, S. T., Goldschmidt, H., & Klein, B. (2010). Growth factors in multiple myeloma: A comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays. BMC Cancer, 10(1), 198. https://doi.org/10.1186/1471-2407-10-198CrossRefPubMedPubMedCentral

138.

Wallace, S. R., Oken, M. M., Lunetta, K. L., Panoskaltsis-Mortari, A., & Masellis, A. M. (2001). Abnormalities of bone marrow mesenchymal cells in multiple myeloma patients. Cancer, 91(7), 1219–1230. https://doi.org/10.1002/1097-0142(20010401)91:7%3c1219::aid-cncr1122%3e3.0.co;2-1CrossRefPubMed

139.

Arnulf, B., Lecourt, S., Soulier, J., Ternaux, B., Lacassagne, M. N., Crinquette, A., Dessoly, J., Sciaini, A. K., Benbunan, M., Chomienne, C., Fermand, J. P., Marolleau, J. P., & Larghero, J. (2007). Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma. Leukemia, 21(1), 158–163. https://doi.org/10.1038/sj.leu.2404466CrossRefPubMed

140.

Tanno, T., Lim, Y., Wang, Q., Chesi, M., Bergsagel, P. L., Matthews, G., Johnstone, R. W., Ghosh, N., Borrello, I., Huff, C. A., & Matsui, W. (2014). Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells. Blood, 123(5), 725–733. https://doi.org/10.1182/blood-2013-08-524025CrossRefPubMedPubMedCentral

141.

Bataille, R., Jourdan, M., Zhang, X. G., & Klein, B. (1989). Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. Journal of Clinical Investigation, 84(6), 2008–2011. https://doi.org/10.1172/JCI114392CrossRefPubMedPubMedCentral

142.

Ludwig, H., Nachbaur, D. M., Fritz, E., Krainer, M., & Huber, H. (1991). Interleukin-6 is a prognostic factor in multiple myeloma. Blood, 77(12), 2794–2795. https://doi.org/10.1182/blood.V77.12.2794.2794CrossRefPubMed

143.

Pelliniemi, T. T., Irjala, K., Mattila, K., Pulkki, K., Rajamaki, A., Tienhaara, A., Laakso, M., & Lahtinen, R. (1995). Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Blood, 85(3), 765–771. https://doi.org/10.1182/blood.V85.3.765.bloodjournal853765CrossRefPubMed

144.

Thaler, J., Fechner, F., Herold, M., & Huber, H. (1994). Interleukin-6 in multiple myeloma: Correlation with disease activity and Ki-67 proliferation index. Leukemia & Lymphoma, 12(3–4), 265–271. https://doi.org/10.3109/10428199409059598CrossRef

145.

Banaszkiewicz, M., Malyszko, J., Batko, K., Koc-Zorawska, E., Zorawski, M., Dumnicka, P., Jurczyszyn, A., Woziwodzka, K., Tisonczyk, J., Krzanowski, M., Malyszko, J., Waszczuk-Gajda, A., Drozdz, R., Kuzniewski, M., & Krzanowska, K. (2020). Evaluating the relationship of GDF-15 with clinical characteristics, cardinal features, and survival in multiple myeloma. Mediators of Inflammation, 5657864. https://doi.org/10.1155/2020/5657864

146.

Alexandrakis, M. G., Passam, F. H., Boula, A., Christophoridou, A., Aloizos, G., Roussou, P., & Kyriakou, D. S. (2003). Relationship between circulating serum soluble interleukin-6 receptor and the angiogenic cytokines basic fibroblast growth factor and vascular endothelial growth factor in multiple myeloma. Annals of Hematology, 82(1), 19–23. https://doi.org/10.1007/s00277-002-0558-0CrossRefPubMed

147.

Corre, J., Labat, E., Espagnolle, N., Hebraud, B., Avet-Loiseau, H., Roussel, M., Huynh, A., Gadelorge, M., Cordelier, P., Klein, B., Moreau, P., Facon, T., Fournie, J. J., Attal, M., & Bourin, P. (2012). Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. Cancer Research, 72(6), 1395–1406. https://doi.org/10.1158/0008-5472.CAN-11-0188CrossRefPubMed

148.

Tarkun, P., Birtas Atesoglu, E., Mehtap, O., Musul, M. M., & Hacihanefioglu, A. (2014). Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients. Acta Haematologica, 131(3), 173–178. https://doi.org/10.1159/000354835CrossRefPubMed

149.

Mei, S., Wang, H., Fu, R., Qu, W., Xing, L., Wang, G., Song, J., Liu, H., Li, L., Wang, X., Wu, Y., Guan, J., Ruan, E., & Shao, Z. (2014). Hepcidin and GDF15 in anemia of multiple myeloma. International Journal of Hematology, 100(3), 266–273. https://doi.org/10.1007/s12185-014-1626-7CrossRefPubMed

150.

Zingone, A., Wang, W., Corrigan-Cummins, M., Wu, S. P., Plyler, R., Korde, N., Kwok, M., Manasanch, E. E., Tageja, N., Bhutani, M., Mulquin, M., Zuchlinski, D., Yancey, M. A., Roschewski, M., Zhang, Y., Roccaro, A. M., Ghobrial, I. M., Calvo, K. R., & Landgren, O. (2014). Altered cytokine and chemokine profiles in multiple myeloma and its precursor disease. Cytokine, 69(2), 294–297. https://doi.org/10.1016/j.cyto.2014.05.017CrossRefPubMedPubMedCentral

151.

Stasi, R., Brunetti, M., Parma, A., Di Giulio, C., Terzoli, E., & Pagano, A. (1998). The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma. Cancer, 82(10), 1860–1866. https://doi.org/10.1002/(SICI)1097-0142(19980515)82:10%3c1860::AID-CNCR7%3e3.0.CO;2-RCrossRefPubMed

152.

Uchiyama, H., Barut, B. A., Mohrbacher, A. F., Chauhan, D., & Anderson, K. C. (1993). Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood, 82(12), 3712–3720. https://doi.org/10.1182/blood.V82.12.3712.3712CrossRefPubMed

153.

Attar-Schneider, O., Zismanov, V., Dabbah, M., Tartakover-Matalon, S., Drucker, L., & Lishner, M. (2016). Multiple myeloma and bone marrow mesenchymal stem cells’ crosstalk: Effect on translation initiation. Molecular Carcinogenesis, 55(9), 1343–1354. https://doi.org/10.1002/mc.22378CrossRefPubMed

154.

Roccaro, A. M., Sacco, A., Maiso, P., Azab, A. K., Tai, Y. T., Reagan, M., Azab, F., Flores, L. M., Campigotto, F., Weller, E., Anderson, K. C., Scadden, D. T., & Ghobrial, I. M. (2013). BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. Journal of Clinical Investigation, 123(4), 1542–1555. https://doi.org/10.1172/JCI66517CrossRefPubMedPubMedCentral

155.

Kanehira, M., Fujiwara, T., Nakajima, S., Okitsu, Y., Onishi, Y., Fukuhara, N., Ichinohasama, R., Okada, Y., & Harigae, H. (2017). An lysophosphatidic acid receptors 1 and 3 axis governs cellular senescence of mesenchymal stromal cells and promotes growth and vascularization of multiple myeloma. Stem Cells, 35(3), 739–753. https://doi.org/10.1002/stem.2499CrossRefPubMed

156.

Urashima, M., Ogata, A., Chauhan, D., Vidriales, M., Teoh, G., Hoshi, Y., Schlossman, R., DeCaprio, J., & Anderson, K. (1996). Interleukin-6 promotes multiple myeloma cell growth via phosphorylation of retinoblastoma protein. Blood, 88(6), 2219–2227. https://doi.org/10.1182/blood.V88.6.2219.bloodjournal8862219CrossRefPubMed

157.

Lokhorst, H. M., Lamme, T., de Smet, M., Klein, S., de Weger, R. A., van Oers, R., & Bloem, A. C. (1994). Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures. Blood, 84(7), 2269–2277. https://doi.org/10.1182/blood.V84.7.2269.2269CrossRefPubMed

158.

Klein, B., Zhang, X. G., Jourdan, M., Content, J., Houssiau, F., Aarden, L., Piechaczyk, M., & Bataille, R. (1989). Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood, 73(2), 517–526. https://doi.org/10.1182/blood.V73.2.517.517CrossRefPubMed

159.

Zhang, X. G., Klein, B., & Bataille, R. (1989). Interleukin-6 is a potent myeloma-cell growth factor in patients with aggressive multiple myeloma. Blood, 74(1), 11–13. https://doi.org/10.1182/blood.V74.1.11.11CrossRefPubMed

160.

Fulciniti, M., Hideshima, T., Vermot-Desroches, C., Pozzi, S., Nanjappa, P., Shen, Z., Patel, N., Smith, E. S., Wang, W., Prabhala, R., Tai, Y. T., Tassone, P., Anderson, K. C., & Munshi, N. C. (2009). A high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma. Clinical Cancer Research, 15(23), 7144–7152. https://doi.org/10.1158/1078-0432.CCR-09-1483CrossRefPubMedPubMedCentral

161.

Teoh, H. K., Chong, P. P., Abdullah, M., Sekawi, Z., Tan, G. C., Leong, C. F., & Cheong, S. K. (2016). Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth. Leukemia Research, 40, 44–53. https://doi.org/10.1016/j.leukres.2015.10.004CrossRefPubMed

162.

Rossi, J. F., Fegueux, N., Lu, Z. Y., Legouffe, E., Exbrayat, C., Bozonnat, M. C., Navarro, R., Lopez, E., Quittet, P., Daures, J. P., Rouille, V., Kanouni, T., Widjenes, J., & Klein, B. (2005). Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: Results of a pilot study including biological aspects. Bone Marrow Transplantation, 36(9), 771–779. https://doi.org/10.1038/sj.bmt.1705138CrossRefPubMedPubMedCentral

163.

Moreau, P., Harousseau, J. L., Wijdenes, J., Morineau, N., Milpied, N., & Bataille, R. (2000). A combination of anti-interleukin 6 murine monoclonal antibody with dexamethasone and high-dose melphalan induces high complete response rates in advanced multiple myeloma. British Journal of Haematology, 109(3), 661–664. https://doi.org/10.1046/j.1365-2141.2000.02093.xCrossRefPubMed

164.

Voorhees, P. M., Manges, R. F., Sonneveld, P., Jagannath, S., Somlo, G., Krishnan, A., Lentzsch, S., Frank, R. C., Zweegman, S., Wijermans, P. W., Orlowski, R. Z., Kranenburg, B., Hall, B., Casneuf, T., Qin, X., van de Velde, H., Xie, H., & Thomas, S. K. (2013). A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. British Journal of Haematology, 161(3), 357–366. https://doi.org/10.1111/bjh.12266CrossRefPubMedPubMedCentral

165.

Brighton, T. A., Khot, A., Harrison, S. J., Ghez, D., Weiss, B. M., Kirsch, A., Magen, H., Gironella, M., Oriol, A., Streetly, M., Kranenburg, B., Qin, X., Bandekar, R., Hu, P., Guilfoyle, M., Qi, M., Nemat, S., & Goldschmidt, H. (2019). Randomized, double-blind, placebo-controlled, multicenter study of siltuximab in high-risk smoldering multiple myeloma. Clinical Cancer Research, 25(13), 3772–3775. https://doi.org/10.1158/1078-0432.CCR-18-3470CrossRefPubMed

166.

Jourdan, M., Tarte, K., Legouffe, E., Brochier, J., Rossi, J. F., & Klein, B. (1999). Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. European Cytokine Network, 10(1), 65–70.PubMedPubMedCentral

167.

Bosseboeuf, A., Allain-Maillet, S., Mennesson, N., Tallet, A., Rossi, C., Garderet, L., Caillot, D., Moreau, P., Piver, E., Girodon, F., Perreault, H., Brouard, S., Nicot, A., Bigot-Corbel, E., Hermouet, S., & Harb, J. (2017). Pro-inflammatory state in monoclonal gammopathy of undetermined significance and in multiple myeloma is characterized by low sialylation of pathogen-specific and other monoclonal immunoglobulins. Frontiers in Immunology, 8, 1347. https://doi.org/10.3389/fimmu.2017.01347CrossRefPubMedPubMedCentral

168.

Tsirakis, G., Pappa, C. A., Spanoudakis, M., Chochlakis, D., Alegakis, A., Psarakis, F. E., Stratinaki, M., Stathopoulos, E. N., & Alexandrakis, M. G. (2012). Clinical significance of sCD105 in angiogenesis and disease activity in multiple myeloma. European Journal of Internal Medicine, 23(4), 368–373. https://doi.org/10.1016/j.ejim.2012.01.012CrossRefPubMed

169.

Schneiderova, P., Pika, T., Gajdos, P., Fillerova, R., Kromer, P., Kudelka, M., Minarik, J., Papajik, T., Scudla, V., & Kriegova, E. (2017). Serum protein fingerprinting by PEA immunoassay coupled with a pattern-recognition algorithms distinguishes MGUS and multiple myeloma. Oncotarget, 8(41), 69408–69421. https://doi.org/10.18632/oncotarget.11242CrossRefPubMed

170.

Merico, F., Bergui, L., Gregoretti, M. G., Ghia, P., Aimo, G., Lindley, I. J., & Caligaris-Cappio, F. (1993). Cytokines involved in the progression of multiple myeloma. Clinical Experimental Immunology, 92(1), 27–31. https://doi.org/10.1111/j.1365-2249.1993.tb05943.xCrossRefPubMedPubMedCentral

171.

Tarantini, S., Balasubramanian, P., Delfavero, J., Csipo, T., Yabluchanskiy, A., Kiss, T., Nyul-Toth, A., Mukli, P., Toth, P., Ahire, C., Ungvari, A., Benyo, Z., Csiszar, A., & Ungvari, Z. (2021). Treatment with the BCL-2/BCL-xL inhibitor senolytic drug ABT263/Navitoclax improves functional hyperemia in aged mice. Geroscience, 43(5), 2427–2440. https://doi.org/10.1007/s11357-021-00440-zCrossRefPubMedPubMedCentral

172.

Pan, J., Li, D., Xu, Y., Zhang, J., Wang, Y., Chen, M., Lin, S., Huang, L., Chung, E. J., Citrin, D. E., Wang, Y., Hauer-Jensen, M., Zhou, D., & Meng, A. (2017). Inhibition of Bcl-2/xl with ABT-263 selectively kills senescent type II pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice. International Journal of Radiation Oncology Biology Physics, 99(2), 353–361. https://doi.org/10.1016/j.ijrobp.2017.02.216CrossRefPubMed

173.

Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., Janakiraman, K., Sharpless, N. E., Ding, S., Feng, W., Luo, Y., Wang, X., Aykin-Burns, N., Krager, K., Ponnappan, U., Hauer-Jensen, M., Meng, A., & Zhou, D. (2016). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicine, 22(1), 78–83. https://doi.org/10.1038/nm.4010CrossRefPubMed

174.

Kim, H. N., Chang, J., Shao, L., Han, L., Iyer, S., Manolagas, S. C., O’Brien, C. A., Jilka, R. L., Zhou, D., & Almeida, M. (2017). DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age. Aging Cell, 16(4), 693–703. https://doi.org/10.1111/acel.12597CrossRefPubMedPubMedCentral

175.

Sharma, A. K., Roberts, R. L., Benson, R. D., Jr., Pierce, J. L., Yu, K., Hamrick, M. W., & McGee-Lawrence, M. E. (2020). The senolytic drug navitoclax (ABT-263) causes trabecular bone loss and impaired osteoprogenitor function in aged mice. Frontiers in Cell and Developmental Biology, 8(354). https://doi.org/10.3389/fcell.2020.00354

176.

Grezella, C., Fernandez-Rebollo, E., Franzen, J., Ventura Ferreira, M. S., Beier, F., & Wagner, W. (2018). Effects of senolytic drugs on human mesenchymal stromal cells. Stem Cell Research & Therapy, 9(1), 108. https://doi.org/10.1186/s13287-018-0857-6CrossRef

177.

Song, X., Dai, J., Li, H., Li, Y., Hao, W., Zhang, Y., Zhang, Y., Su, L., & Wei, H. (2019). Anti-aging effects exerted by Tetramethylpyrazine enhances self-renewal and neuronal differentiation of rat bMSCs by suppressing NF-kB signaling. Bioscience Reports, 39(6). https://doi.org/10.1042/BSR20190761

178.

Gao, B., Lin, X., Jing, H., Fan, J., Ji, C., Jie, Q., Zheng, C., Wang, D., Xu, X., Hu, Y., Lu, W., Luo, Z., & Yang, L. (2018). Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti-inflammatory and angiogenic environment in aging mice. Aging Cell, 17(3), e12741. https://doi.org/10.1111/acel.12741CrossRefPubMedPubMedCentral

179.

Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., O’Hara, S. P., LaRusso, N. F., Miller, J. D., Roos, C. M., Verzosa, G. C., LeBrasseur, N. K., Wren, J. D., Farr, J. N., Khosla, S., Stout, M. B., et al. (2015). The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell, 14(4), 644–658. https://doi.org/10.1111/acel.12344CrossRefPubMedPubMedCentral

180.

Farr, J. N., Xu, M., Weivoda, M. M., Monroe, D. G., Fraser, D. G., Onken, J. L., Negley, B. A., Sfeir, J. G., Ogrodnik, M. B., Hachfeld, C. M., LeBrasseur, N. K., Drake, M. T., Pignolo, R. J., Pirtskhalava, T., Tchkonia, T., Oursler, M. J., Kirkland, J. L., & Khosla, S. (2017). Targeting cellular senescence prevents age-related bone loss in mice. Nature Medicine, 23(9), 1072–1079. https://doi.org/10.1038/nm.4385CrossRefPubMedPubMedCentral

181.

Hickson, L. J., Langhi Prata, L. G. P., Bobart, S. A., Evans, T. K., Giorgadze, N., Hashmi, S. K., Herrmann, S. M., Jensen, M. D., Jia, Q., Jordan, K. L., Kellogg, T. A., Khosla, S., Koerber, D. M., Lagnado, A. B., Lawson, D. K., LeBrasseur, N. K., Lerman, L. O., McDonald, K. M., McKenzie, T. J., Passos, J. F., et al. (2019). Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease. eBioMedicine, 47, 446–456. https://doi.org/10.1016/j.ebiom.2019.08.069CrossRefPubMedPubMedCentral

182.

Justice, J. N., Nambiar, A. M., Tchkonia, T., LeBrasseur, N. K., Pascual, R., Hashmi, S. K., Prata, L., Masternak, M. M., Kritchevsky, S. B., Musi, N., & Kirkland, J. L. (2019). Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. eBioMedicine, 40, 554–563. https://doi.org/10.1016/j.ebiom.2018.12.052CrossRefPubMedPubMedCentral

183.

Thaler, J., Fechner, F., Herold, M., & Huber, H. (1994). Interleukin-6 in multiple myeloma: Correlation with disease activity and Ki-67 proliferation index. Leukaemia & Lymphoma, 12(3–4), 265–271. https://doi.org/10.3109/10428199409059598CrossRef

184.

185.

Bonilla, X., Vanegas, N. P., & Vernot, J. P. (2019). Acute leukemia induces senescence and impaired osteogenic differentiation in mesenchymal stem cells endowing leukemic cells with functional advantages. Stem Cells International, 2019, 3864948. https://doi.org/10.1155/2019/3864948CrossRefPubMedPubMedCentral

Titel: Mesenchymal stromal cell senescence in haematological malignancies
verfasst von: Natalya Plakhova
Vasilios Panagopoulos
Kate Vandyke
Andrew C. W. Zannettino
Krzysztof M. Mrozik
Publikationsdatum: 09.01.2023
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 1/2023
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-022-10069-9

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Mesenchymal stromal cell senescence in haematological malignancies

Abstract

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2023

Autophagy, molecular chaperones, and unfolded protein response as promoters of tumor recurrence

KISS1 metastasis suppressor in tumor dormancy: a potential therapeutic target for metastatic cancers?

Newly identified form of phenotypic plasticity of cancer: immunogenic mimicry

Involvement of redox signalling in tumour cell dormancy and metastasis

Regulation of dormancy during tumor dissemination: the role of the ECM

The genetic profile and molecular subtypes of human pseudomyxoma peritonei and appendiceal mucinous neoplasms: a systematic review

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Onkologie