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Myelodysplastic syndrome

Transforming growth factor (TGF)-β pathway as a therapeutic target in lower risk myelodysplastic syndromes

Leukemia volume 33, pages 1303–1312 (2019)Cite this article

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Abstract

The transforming growth factor (TGF)-β superfamily comprises more than 30 soluble growth factors that play a central role in erythropoiesis and are part of a tightly regulated myelosuppressive negative feedback loop under physiologic conditions. TGF-β receptor activation and phosphorylation trigger a regulatory circuit of activating and inhibitory SMAD proteins and increased activation of the TGF-β signaling pathway either by a loss of negative feedback or constitutive activation has been associated with the myelosuppression and ineffective erythropoiesis in myelodysplastic syndromes (MDS). Anemia is the predominant cause of morbidity and quality of life impairment in patients with lower-risk (LR)-MDS, and there are very limited therapy options for these patients after failure of erythropoiesis stimulating agents (ESAs). Targeting the aberrant TGF-ß signaling pathway has therefore been investigated as a promising therapeutic approach to resolve the ineffective erythropoiesis in LR-MDS. In this article, we provide a brief overview of the TGF-β signaling cascade in hematopoiesis under physiologic conditions and its role in MDS pathogenesis. We also review preclinical and clinical data for the activin receptor type IIA ligand traps sotatercept and luspatercept that have recently shown promising results in overcoming the myelosuppressive effects of TGF-β signaling alterations to improve hematopoiesis in transfusion-dependent, non-del(5q) LR-MDS patients. Additional potential targets within the TGF-β pathway have also been identified in preclinical experiments and may provide further therapeutic options. Finally, combining different TGF-β pathway inhibitors or using them in combination with ESAs or the immunomodulator lenalidomide might have synergistic effects as well.

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References

  1. Stahl M, Zeidan AM. Management of lower-risk myelodysplastic syndromes without del5q: current approach and future trends. Expert Rev Hematol. 2017;10:345–64.

    PubMed  CAS  Google Scholar 

  2. Steensma DP. Myelodysplastic syndromes current treatment algorithm 2018. Blood Cancer J. 2018;8:47.

    PubMed  PubMed Central  Google Scholar 

  3. Giagounidis A. Current treatment algorithm for the management of lower-risk MDS. Hematol Am Soc Hematol Educ Program. 2017;2017:453–9.

    Google Scholar 

  4. Greenberg PL, Stone RM, Al-Kali A, Barta SK, Bejar R, Bennett JM, et al. Myelodysplastic syndromes, version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15:60–87.

    PubMed  Google Scholar 

  5. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65.

    PubMed  PubMed Central  CAS  Google Scholar 

  6. Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004;104:579–85.

    PubMed  CAS  Google Scholar 

  7. Ball B, Zeidan A, Gore SD, Prebet T. Hypomethylating agent combination strategies in myelodysplastic syndromes: hopes and shortcomings. Leuk Lymphoma. 2017;58:1022–36.

    PubMed  CAS  Google Scholar 

  8. Fenaux P, Ades L. How we treat lower-risk myelodysplastic syndromes. Blood. 2013;121:4280–6.

    PubMed  CAS  Google Scholar 

  9. Bejar R, Papaemmanuil E, Haferlach T, Garcia-Manero G, Maciejewski JP, Sekeres MA, et al. Somatic mutations in MDS patients are associated with clinical features and predict prognosis independent of the IPSS-R: analysis of combined datasets from the International Working Group for prognosis in MDS-molecular committee. Blood. 2015;126:907.

    Google Scholar 

  10. Platzbecker U. Treatment of MDS. Blood. 2019;133:1096–1107.

  11. Stahl M, DeVeaux M, de Witte T, Neukirchen J, Sekeres MA, Brunner AM, et al. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort. Blood Adv. 2018;2:1765–72.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017;18:1338–47.

    PubMed  CAS  Google Scholar 

  13. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355:1456–65.

    PubMed  CAS  Google Scholar 

  14. Zeidan AM, Al Ali NH, Padron E, Lancet J, List A, Komrokji RS. Lenalidomide treatment for lower risk nondeletion 5q myelodysplastic syndromes patients yields higher response rates when used before azacitidine. Clin Lymphoma Myeloma Leuk. 2015;15:705–10.

    PubMed  Google Scholar 

  15. Mies A, Platzbecker U. Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-beta superfamily inhibitors. Semin Hematol. 2017;54:141–6.

    PubMed  Google Scholar 

  16. Kelaidi C, Park S, Sapena R, Beyne-Rauzy O, Coiteux V, Vey N, et al. Long-term outcome of anemic lower-risk myelodysplastic syndromes without 5q deletion refractory to or relapsing after erythropoiesis-stimulating agents. Leukemia. 2013;27:1283–90.

    PubMed  CAS  Google Scholar 

  17. Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J, et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017;31:1944–50.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Park S, Fenaux P, Greenberg P, Mehta B, Callaghan F, Kim C, et al. Efficacy and safety of darbepoetin alpha in patients with myelodysplastic syndromes: a systematic review and meta-analysis. Br J Haematol. 2016;174:730–47.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Zeidan AM, Giri S, DeVeaux M, Ballas SK, Duong VH. Systematic review and meta-analysis of the effect of iron chelation therapy on overall survival and disease progression in patients with lower-risk myelodysplastic syndromes. Ann Hematol. 2019;98:339–50.

  20. Park S, Kelaidi C, Sapena R, Vassilieff D, Beyne-Rauzy O, Coiteux V, et al. Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res. 2010;34:1430–6.

    PubMed  Google Scholar 

  21. Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, et al. The medalist trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept to treat anemia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions. Blood. 2018;132(Suppl 1):1.

    Google Scholar 

  22. Komrokji R, Garcia-Manero G, Ades L, Prebet T, Steensma DP, Jurcic JG, et al. Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Lancet Haematol. 2018;5:e63–e72.

    PubMed  Google Scholar 

  23. Muench DE, Ferchen K, Velu CS, Pradhan K, Chetal K, Chen X, et al. SKI controls MDS-associated chronic TGF-beta signaling, aberrant splicing, and stem cell fitness. Blood. 2018;132:e24–e34.

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Zermati Y, Fichelson S, Valensi F, Freyssinier JM, Rouyer-Fessard P, Cramer E, et al. Transforming growth factor inhibits erythropoiesis by blocking proliferation and accelerating differentiation of erythroid progenitors. Exp Hematol. 2000;28:885–94.

    PubMed  CAS  Google Scholar 

  25. Blank U, Karlsson S. TGF-beta signaling in the control of hematopoietic stem cells. Blood. 2015;125:3542–50.

    PubMed  CAS  Google Scholar 

  26. Larsson J, Karlsson S. The role of Smad signaling in hematopoiesis. Oncogene. 2005;24:5676–92.

    PubMed  CAS  Google Scholar 

  27. Blank U, Karlsson S. The role of Smad signaling in hematopoiesis and translational hematology. Leukemia. 2011;25:1379–88.

    PubMed  CAS  Google Scholar 

  28. Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, et al. Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell. 2011;147:1146–58.

    PubMed  CAS  Google Scholar 

  29. Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, et al. Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med. 2014;20:1321–6.

    PubMed  CAS  Google Scholar 

  30. He W, Dorn DC, Erdjument-Bromage H, Tempst P, Moore MA, Massague J. Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell. 2006;125:929–41.

    PubMed  CAS  Google Scholar 

  31. Zhou L, McMahon C, Bhagat T, Alencar C, Yu Y, Fazzari M, et al. Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase. Cancer Res. 2011;71:955–63.

    PubMed  CAS  Google Scholar 

  32. Bhagat TD, Zhou L, Sokol L, Kessel R, Caceres G, Gundabolu K, et al. miR-21 mediates hematopoietic suppression in MDS by activating TGF-beta signaling. Blood. 2013;121:2875–81.

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Bachegowda L, Gligich O, Mantzaris I, Schinke C, Wyville D, Carrillo T, et al. Signal transduction inhibitors in treatment of myelodysplastic syndromes. J Hematol Oncol. 2013;6:50.

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, et al. Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20:408–14.

    PubMed  CAS  Google Scholar 

  35. Massagué J. TGFβ signalling in context. Nat Rev Mol Cell Biol. 2012;13:616.

    PubMed  PubMed Central  Google Scholar 

  36. Chapnick DA, Warner L, Bernet J, Rao T, Liu X. Partners in crime: the TGFβ and MAPK pathways in cancer progression. Cell Biosci. 2011;1:42.

  37. Wolfraim LA, Fernandez TM, Mamura M, Fuller WL, Kumar R, Cole DE, et al. Loss of Smad3 in acute T-cell lymphoblastic leukemia. N Engl J Med. 2004;351:552–9.

    PubMed  CAS  Google Scholar 

  38. Imai Y, Kurokawa M, Izutsu K, Hangaishi A, Maki K, Ogawa S, et al. Mutations of the Smad4 gene in acute myelogeneous leukemia and their functional implications in leukemogenesis. Oncogene. 2001;20:88–96.

    PubMed  CAS  Google Scholar 

  39. Grady WM, Myeroff LL, Swinler SE, Rajput A, Thiagalingam S, Lutterbaugh JD, et al. Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. Cancer Res. 1999;59:320–4.

    PubMed  CAS  Google Scholar 

  40. Malcovati L, Karimi M, Papaemmanuil E, Ambaglio I, Jadersten M, Jansson M, et al. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood. 2015;126:233–41.

    PubMed  PubMed Central  CAS  Google Scholar 

  41. Haferlach T, Nagata Y, Grossmann V, Okuno Y, Bacher U, Nagae G, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28:241–7.

    PubMed  CAS  Google Scholar 

  42. Jin S, Su H, Tran NT, Song J, Lu SS, Li Y, et al. Splicing factor SF3B1K700E mutant dysregulates erythroid differentiation via aberrant alternative splicing of transcription factor TAL1. PLoS ONE. 2017;12:e0175523.

    PubMed  PubMed Central  Google Scholar 

  43. Malcovati L, Cazzola M. Refractory anemia with ring sideroblasts. Best Pract Res Clin Haematol. 2013;26:377–85.

    PubMed  CAS  Google Scholar 

  44. Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011;365:1384–95.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Mortera-Blanco T, Dimitriou M, Woll PS, Karimi M, Elvarsdottir E, Conte S, et al. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells. Blood. 2017;130:881–90.

    PubMed  PubMed Central  CAS  Google Scholar 

  46. Bejar R. Implications of molecular genetic diversity in myelodysplastic syndromes. Curr Opin Hematol. 2017;24:73–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  47. Zhou L, Nguyen AN, Sohal D, Ying Ma J, Pahanish P, Gundabolu K, et al. Inhibition of the TGF-beta receptor I kinase promotes hematopoiesis in MDS. Blood. 2008;112:3434–43.

    PubMed  PubMed Central  CAS  Google Scholar 

  48. Valcarcel D, Verma A, Platzbecker U, Santini V, Giagounidis A, Díez-Campelo M, et al. Phase 2 study of monotherapy galunisertib (LY2157299 monohydrate) in very low-, low-, and intermediate-risk patients with myelodysplastic syndromes. Blood. 2015;126:1669.

    Google Scholar 

  49. Attie KM, Allison MJ, McClure T, Boyd IE, Wilson DM, Pearsall AE, et al. A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers. Am J Hematol. 2014;89:766–70.

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Bose P, Verstovsek S. Management of myelofibrosis-related cytopenias. Curr Hematol Malig Rep. 2018;13:164–72.

    PubMed  Google Scholar 

  51. Motta I, Scaramellini N, Cappellini MD. Investigational drugs in phase I and phase II clinical trials for thalassemia. Expert Opin Investig Drugs. 2017;26:793–802.

    PubMed  CAS  Google Scholar 

  52. Santini V, Almeida A, Giagounidis A, Gropper S, Jonasova A, Vey N, et al. Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents. J Clin Oncol. 2016;34:2988–96.

    PubMed  CAS  Google Scholar 

  53. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–25.

    PubMed  CAS  Google Scholar 

  54. National Comprehensive Cancer Network. NCCN Guidelines Version 2. 2019: Myelodysplastic syndromes 2019. https://www.nccn.org/store/login/login.aspx?ReturnURL=https%3a%2f%2fwww.nccn.org%2fprofessionals%2fphysician_gls%2fPDF%2fmds.pdf.

  55. Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118:3765–76.

    PubMed  CAS  Google Scholar 

  56. Jabbour E, Short NJ, Montalban-Bravo G, Huang X, Bueso-Ramos C, Qiao W, et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood. 2017;130:1514–22.

    PubMed  PubMed Central  CAS  Google Scholar 

  57. Tobiasson M, Dybedahl I, Holm MS, Karimi M, Brandefors L, Garelius H, et al. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial. Blood. Cancer J. 2014;4:e189.

    CAS  Google Scholar 

  58. Thepot S, Ben Abdelali R, Chevret S, Renneville A, Beyne-Rauzy O, Prebet T, et al. A randomized phase II trial of azacitidine+/- epoetin-beta in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents. Haematologica. 2016;101:918–25.

    PubMed  PubMed Central  CAS  Google Scholar 

  59. Komrokji R, Swern AS, Grinblatt D, Lyons RM, Tobiasson M, Silverman LR, et al. Azacitidine in lower-risk myelodysplastic syndromes: a meta-analysis of data from prospective studies. Oncologist. 2018;23:159–70.

    PubMed  Google Scholar 

  60. Zeidan AM, Zhu W, Wang R, Stahl M, Huntington SF, Giri S, et al. Transfusion independence in lower-risk, Non-del5(q) myelodysplastic syndromes (LR-MDS) among patients (pts) initiating hypomethylating agents (HMAs) while receiving red blood cell (RBC) transfusions. Blood. 2018;132(Suppl 1):838.

    Google Scholar 

  61. Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL, et al. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009;27:1850–6.

    PubMed  CAS  Google Scholar 

  62. Sherman ML, Borgstein NG, Mook L, Wilson D, Yang Y, Chen N, et al. Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women. J Clin Pharmacol. 2013;53:1121–30.

    PubMed  CAS  Google Scholar 

  63. Raftopoulos H, Laadem A, Hesketh PJ, Goldschmidt J, Gabrail N, Osborne C, et al. Sotatercept (ACE-011) for the treatment of chemotherapy-induced anemia in patients with metastatic breast cancer or advanced or metastatic solid tumors treated with platinum-based chemotherapeutic regimens: results from two phase 2 studies. Support Care Cancer. 2016;24:1517–25.

    PubMed  Google Scholar 

  64. Abdulkadyrov KM, Salogub GN, Khuazheva NK, Sherman ML, Laadem A, Barger R, et al. Sotatercept in patients with osteolytic lesions of multiple myeloma. Br J Haematol. 2014;165:814–23.

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Carrancio S, Markovics J, Wong P, Leisten J, Castiglioni P, Groza MC, et al. An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin. Br J Haematol. 2014;165:870–82.

    PubMed  PubMed Central  CAS  Google Scholar 

  66. Garcia-Manero G, Gore SD, Cogle C, Ward R, Shi T, Macbeth KJ, et al. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29:2521–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  67. Garcia-Manero G, Gore SD, Kambhampati S, Scott B, Tefferi A, Cogle CR, et al. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016;30:889–96.

    PubMed  PubMed Central  CAS  Google Scholar 

  68. Savona MR, Kolibaba K, Conkling P, Kingsley EC, Becerra C, Morris JC, et al. Extended dosing with CC-486 (oral azacitidine) in patients with myeloid malignancies. Am J Hematol. 2018;93:1199–1206.

  69. Steensma DP. How I use molecular genetic tests to evaluate patients who have or may have myelodysplastic syndromes. Blood. 2018;132:1657–63.

    PubMed  CAS  Google Scholar 

  70. Pardanani A, Finke C, Lasho TL, Al-Kali A, Begna KH, Hanson CA, et al. IPSS-independent prognostic value of plasma CXCL10, IL-7 and IL-6 levels in myelodysplastic syndromes. Leukemia. 2012;26:693–9.

    PubMed  CAS  Google Scholar 

  71. Hsu HC, Lee YM, Tsai WH, Jiang ML, Ho CH, Ho CK, et al. Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome. Oncology. 2002;63:64–9.

    PubMed  CAS  Google Scholar 

  72. Loffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermuller J, Kretzschmar AK, et al. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood. 2007;110:1330–3.

    PubMed  Google Scholar 

  73. Lam J, van den Bosch M, Wegrzyn J, Parker J, Ibrahim R, Slowski K, et al. miR-143/145 differentially regulate hematopoietic stem and progenitor activity through suppression of canonical TGFbeta signaling. Nat Commun. 2018;9:2418.

    PubMed  PubMed Central  Google Scholar 

  74. Scullen T, Santo L, Vallet S, Fulciniti M, Eda H, Cirstea D, et al. Lenalidomide in combination with an activin A-neutralizing antibody: preclinical rationale for a novel anti-myeloma strategy. Leukemia. 2013;27:1715–21.

    PubMed  CAS  Google Scholar 

  75. Terpos E, Kastritis E, Christoulas D, Gkotzamanidou M, Eleutherakis-Papaiakovou E, Kanellias N, et al. Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy. Ann Oncol. 2012;23:2681–6.

    PubMed  CAS  Google Scholar 

  76. Stahl M, Zeidan AM. Lenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications. Cancer. 2017;123:1703–13.

    PubMed  CAS  Google Scholar 

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Acknowledgements

Amer Zeidan is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a NCI’s Cancer Clinical Investigator Team Leadership Award (CCITLA). Research reported in this publication was supported in part  by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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A.M.Z. received research funding (institutional) from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics. A.M.Z. had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Ariad, Cardinal Health, Beyond Spring, Seattle Genetics, and Takeda. A.M.Z. received honoraria from and was a speaker for Takeda (past). A.M.Z. is one of the MEDALIST investigators. None of these relationships were related to the development of this manuscript. The other author declares that he has no conflict of interest.

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Bewersdorf, J.P., Zeidan, A.M. Transforming growth factor (TGF)-β pathway as a therapeutic target in lower risk myelodysplastic syndromes. Leukemia 33, 1303–1312 (2019). https://doi.org/10.1038/s41375-019-0448-2

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