The synergistic antileukemic effects of eltrombopag and decitabine in myeloid leukemia cells

References

• Klepin HD. Myelodysplastic syndromes and acute myeloid leukemia in the elderly. Clin Geriatr Med. 2016;32:155–173. doi:10.1016/j.cger.2015.08.01026614866
   PubMed Web of Science ®Google Scholar
• Santini V. How I treat MDS after hypomethylating agent failure. Blood. 2019;133:521–529. doi:10.1182/blood-2018-03-78591530545832
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Hu X. Hypomethylating agent therapy use and survival in older patients with chronic myelomonocytic leukemia in the united states: A large population-based study. Cancer. 2017;123:3754–3762. doi:10.1002/cncr.3081428621841
   PubMed Web of Science ®Google Scholar
• Malik P, Cashen AF. Decitabine in the treatment of acute myeloid leukemia in elderly patients. Cancer Manag Res. 2014;6:53–61. doi:10.2147/CMAR.S4060024520204
   PubMed Web of Science ®Google Scholar
• Cruijsen M, Lubbert M, Wijermans P, Huls G. Clinical results of hypomethylating agents in aml treatment. J Clin Med. 2014;4:1–17. doi:10.3390/jcm401000126237015
   PubMed Web of Science ®Google Scholar
• Cashen AF, Schiller GJ, O’Donnell MR, DiPersio JF. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28(4):556–561. doi:10.1200/JCO.2009.23.917820026803
   PubMed Web of Science ®Google Scholar
• Gotze K, Muller-Thomas C, Peschel C. The role of azacitidine in the management of myelodysplastic syndromes (mds). Cancer Manag Res. 2009;1:119–130.21188130
   PubMedGoogle Scholar
• DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133:7–17. doi:10.1182/blood-2018-08-86875230361262
   PubMed Web of Science ®Google Scholar
• Gao C, Wang J, Li Y, et al. Incidence and risk of hematologic toxicities with hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukopenia: A systematic review and meta-analysis. Medicine. 2018;97:e11860. doi:10.1097/MD.000000000001186030142779
   PubMed Web of Science ®Google Scholar
• Bryan J, Jabbour E, Prescott H, Kantarjian H. Thrombocytopenia in patients with myelodysplastic syndromes. Semin Hematol. 2010;47:274–280. doi:10.1053/j.seminhematol.2010.02.00620620439
   PubMed Web of Science ®Google Scholar
• Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20:2429–2440. doi:10.1200/JCO.2002.04.11712011120
   PubMed Web of Science ®Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–232. doi:10.1016/S1470-2045(09)70234-719230772
   PubMed Web of Science ®Google Scholar
• Svensson T, Chowdhury O, Garelius H, et al. A pilot phase i dose finding safety study of the thrombopoietin-receptor agonist, eltrombopag, in patients with myelodysplastic syndrome treated with azacitidine. Eur J Haematol. 2014;93:439–445. doi:10.1111/ejh.1238324853277
   PubMed Web of Science ®Google Scholar
• Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012;367:11–19. doi:10.1056/NEJMoa120093122762314
   PubMed Web of Science ®Google Scholar
• Will B, Kawahara M, Luciano JP, et al. Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood. 2009;114:3899–3908. doi:10.1182/blood-2009-04-21949319710504
   PubMed Web of Science ®Google Scholar
• Kalota A, Gewirtz AM. A prototype nonpeptidyl, hydrazone class, thrombopoietin receptor agonist, sb-559457, is toxic to primary human myeloid leukemia cells. Blood. 2010;115:89–93. doi:10.1182/blood-2009-06-22775119880492
   PubMed Web of Science ®Google Scholar
• Erickson-Miller CL, Kirchner J, Aivado M, May R, Payne P, Chadderton A. Reduced proliferation of non-megakaryocytic acute myelogenous leukemia and other leukemia and lymphoma cell lines in response to eltrombopag. Leuk Res. 2010;34:1224–1231. doi:10.1016/j.leukres.2010.02.00520202683
   PubMed Web of Science ®Google Scholar
• Roth M, Will B, Simkin G, et al. Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood. 2012;120:386–394. doi:10.1182/blood-2011-12-39966722627766
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Sockel K, Schonefeldt C, et al. Induction of short-term remission with single agent eltrombopag in refractory nucleophosmin-1-mutated acute myeloid leukemia. Haematologica. 2014;99:e247–e248. doi:10.3324/haematol.2014.11194825193964
   PubMed Web of Science ®Google Scholar
• Tamari R, Schinke C, Bhagat T, et al. Eltrombopag can overcome the anti-megakaryopoietic effects of lenalidomide without increasing proliferation of the malignant myelodysplastic syndrome/acute myelogenous leukemia clone. Leukemia Lymphoma. 2014;55:2901–2906. doi:10.3109/10428194.2014.89418624650011
   PubMed Web of Science ®Google Scholar
• Kalota A, Selak MA, Garcia-Cid LA, Carroll M. Eltrombopag modulates reactive oxygen species and decreases acute myeloid leukemia cell survival. PLoS One. 2015;10:e0126691. doi:10.1371/journal.pone.012669125915523
   PubMed Web of Science ®Google Scholar
• Hole PS, Pearn L, Tonks AJ, et al. Ras-induced reactive oxygen species promote growth factor-independent proliferation in human cd34+ hematopoietic progenitor cells. Blood. 2010;115:1238–1246. doi:10.1182/blood-2009-12-25599220007804
   PubMed Web of Science ®Google Scholar
• Brodska B, Holoubek A. Generation of reactive oxygen species during apoptosis induced by DNA-damaging agents and/or histone deacetylase inhibitors. Oxid Med Cell Longev. 2011;2011:253529. doi:10.1155/2011/25352921949898
   PubMed Web of Science ®Google Scholar
• Shin DY, Park YS, Yang K, et al. Decitabine, a DNA methyltransferase inhibitor, induces apoptosis in human leukemia cells through intracellular reactive oxygen species generation. Int J Oncol. 2012;41:910–918. doi:10.3892/ijo.2012.154622767021
   PubMed Web of Science ®Google Scholar
• Fandy TE, Jiemjit A, Thakar M, Rhoden P, Suarez L, Gore SD. Decitabine induces delayed reactive oxygen species (ros) accumulation in leukemia cells and induces the expression of ros generating enzymes. Clin Cancer Res. 2014;20:1249–1258. doi:10.1158/1078-0432.CCR-13-304524423613
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Wong RS, Verma A, et al. Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: A multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial. Lancet Haematol. 2015;2:e417–e426. doi:10.1016/S2352-3026(15)00149-026686043
   PubMed Web of Science ®Google Scholar
• Mittelman M, Platzbecker U, Afanasyev B, et al. Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (aspire): A randomised, placebo-controlled, phase 2 trial. Lancet Haematol. 2018;5:e34–e43. doi:10.1016/S2352-3026(17)30228-429241762
   PubMed Web of Science ®Google Scholar
• Cole S, Benard L, Carvajal LA, et al. Pre-clinical modeling of concomitant therapy with azacytidine and eltrombopag in MDS/AML. Blood. 2017;130:2950.
   Web of Science ®Google Scholar
• Buckstein R. Eltrombopag use in higher risk myeloid cancers: fitting a square “pag” into a round hole? Lancet Haematol. 2019;6:e111–e112. doi:10.1016/S2352-3026(19)30010-930704924
   PubMed Web of Science ®Google Scholar
• Sangkhae V, Etheridge SL, Kaushansky K, Hitchcock IS. The thrombopoietin receptor, mpl, is critical for development of a jak2v617f-induced myeloproliferative neoplasm. Blood. 2014;124:3956–3963. doi:10.1182/blood-2014-07-58723825339357
   PubMed Web of Science ®Google Scholar
• Li H, Zhao N, Li Y, et al. c-MPL is a candidate surface marker and confers self-renewal, quiescence, chemotherapy resistance, and leukemia initiation potential in leukemia stem cells. Stem Cells. 2018;36:1685–1696.30106501
   PubMed Web of Science ®Google Scholar
• Dickinson M, Cherif H, Fenaux P, et al. Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk mds with thrombocytopenia. Blood. 2018;132:2629–2638. doi:10.1182/blood-2018-06-85522130305280
   PubMed Web of Science ®Google Scholar
• Zhou H, Hou Y, Liu X, et al. Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia. Thromb Haemost. 2015;113:1021–1034. doi:10.1160/TH14-04-034225566808
   PubMed Web of Science ®Google Scholar