Novel treatments to tackle myelofibrosis

References

• Barosi G, Mesa RA, Thiele J, et al. International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22:437–438.
   PubMed Web of Science ®Google Scholar
• Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification and management. Am J Hematol. 2016;91:1262–1271.
   PubMed Web of Science ®Google Scholar
• Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129(6):667–679.
   PubMed Web of Science ®Google Scholar
• Vannucchi AM, Lasho TL, Guglielmelli P, et al. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013;27:1861–1869.
   PubMed Web of Science ®Google Scholar
• Guglielmelli P, Lasho TL, Rotunno G, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia. 2014;28:1804–1810.
   PubMed Web of Science ®Google Scholar
• Tefferi A, Guglielmelli P, Lasho TL, et al. CALR and ASXL1 mutation-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia. 2014;28:1494–1500.
   PubMed Web of Science ®Google Scholar
• Harutyunyan A, Klampfl T, Cazzola M, et al. p53 lesions in leukemic transformation. N Engl J Med. 2011;364(5):488–490.
   PubMed Web of Science ®Google Scholar
• Rampal R, Ahn J, Abdel-Wahab O, et al. Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms. Proc Natl Acad Sci. 2014;111(50):e5401–e5410.
   PubMed Web of Science ®Google Scholar
• Barbui T, Tefferi A, Vannucchi AR, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32(5):1057–1069.
   PubMed Web of Science ®Google Scholar
• Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895–2901.
   PubMed Web of Science ®Google Scholar
• Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study of the IWG-MRT (International Working Group for Myelofibrosis Research and Treatment). Blood. 2010;115:1703–1708.
   PubMed Web of Science ®Google Scholar
• Gangat N, Caramazza D, Vaidya R, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count and transfusion status. J Clin Oncol. 2011;29:392–397.
   PubMed Web of Science ®Google Scholar
• Guglielmelli P, Lasho TL, Rotunno G, et al. MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2017;36(4):310–318.
   PubMed Web of Science ®Google Scholar
• Tefferi A, Guglielmelli P, Nicolosi M, et al. GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia. 2018;32(7):1631–1642.
   PubMed Web of Science ®Google Scholar
• Vannucchi AM, Harrison CN. Emerging treatments for classical myeloproliferative neoplasms. Blood. 2017;129(6):693–702.
   PubMed Web of Science ®Google Scholar
• Tremblay D, Marcellino B, Mascarenhas J. Pharmacotherapy of myelofibrosis. Drugs. 2017;77:1549–1563.
   PubMed Web of Science ®Google Scholar
• Pettit K, Odenike O. Novel therapies for myelofibrosis. Curr Hematol Malig Rep. 2017;12:611–624.
   PubMed Web of Science ®Google Scholar
• Shreenivas A, Mascarenhas J. Emerging drugs for the treatment of myelofibrosis. Exp Opin Emerging Drugs. 2018;23(1):37–49.
   PubMed Web of Science ®Google Scholar
• Harrington PM, Harrison CN. Beyond JAK-2: potential targets for myeloproliferative neoplasm therapy. Exp Rev Hematol. 2018;11(4):315–324.
   PubMed Web of Science ®Google Scholar
• Bose P, Verstovsek S. Investigational histone deacetylase inhibitors (HDACi) in myeloproliferative neoplasms. Exp Opin Investg Drugs. 2016;25(12):1393–1403.
   PubMed Web of Science ®Google Scholar
• Tefferi A, Al-Ali HK, Barosi G, et al. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia. 2017;31(5):1252.
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Eng J Med. 2012;366(9):799–807.
   PubMed Web of Science ®Google Scholar
• Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Eng J Med. 2012;366(9):787–798.
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Gotlib J, Mesa R, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10:156.
   PubMed Web of Science ®Google Scholar
• Marti-Carvajal AJ, Anand V, Sola I. Janus kinase-1 and Janus kinase-2 inhibitors for treating myelofibrosis. Cochrane Database Syst Rev. 2015;4:CD010298.
   Google Scholar
• Cervantes F, Pereira A. Does ruxolitinib prolong the survival of patients with myelofibrosis? Blood. 2017;129(7):832–837.
   PubMed Web of Science ®Google Scholar
• Porpaczy E, Tripolt S, Hoelbl-Kovacic A, et al. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy. Blood. 2018;132(7):694–706.
   PubMed Web of Science ®Google Scholar
• Mesa RA, Cortes J. Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. J Hematol Oncol. 2013;6:79.
   PubMed Web of Science ®Google Scholar
• Talpz M, Paquette R, Afrin L, et al. Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. J Hematol Oncol. 2013;6:81.
   PubMed Web of Science ®Google Scholar
• Grunwald MR, Spivak JL. Ruxolitinib enhances platelet production in patients with thrombocytopenic myelofibrosis. J Clin Oncol. 2014;32:2013–2015.
   Google Scholar
• Bjorn ME, Holmstrom MO, Hasselbalch HC, et al. Ruxolitinib is manageable in patients with myelofibrosis and severe thrombocytopenia: a report on 12 Danish patients. Leuk Lymph. 2016;57(1):125–128.
   PubMed Web of Science ®Google Scholar
• Ellis MH, Lavi N, Mischenko E, et al. Ruxolitinib treatment for myelofibrosis: efficacy and tolerability in routine practice. Leukemia Res. 2015;39:1154–1158.
   Web of Science ®Google Scholar
• Bjorn ME, Hasselbalch HC. Minimal residual disease or cure in MPNs? Rationales and perspectives on combination therapy with interferon-alpha2 and ruxolitinib. Exp Rev Hematol. 2017;10(5):393–404.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Tong W, Kantarjian H, et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia. 2008;22:965–970.
   PubMed Web of Science ®Google Scholar
• Thepot S, Itzykson R, Seegers V, et al. Treatment of progression of Philadelphia-negtive myeloproliferative neoplasms to myelodysplastic syndromes or actue myeloid leukemia by azacitidine: a report on 54 cases on behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood. 2010;116(19):3735–3742.
   PubMed Web of Science ®Google Scholar
• Daver N, Cortes JE, Pemmaraju N, et al. Ruxolitinib (RUX) in combination with 5-azacytidine (AZA) as therapy for patients (pts) with myelofibrosis (MF). Am Soc Hematol Annu Meet Exposition, Blood, San Diego, Ca. 2016;128:1127.
   Google Scholar
• Joy Ho P, Bajel A, Burbury K, et al. A case-based discussion of clinical problems in the management of patients treated with ruxolitinib for myelofibrosis. Intern Med J. 2017;47(3):262–268.
   PubMed Web of Science ®Google Scholar
• Komrokji RS, Seymour JF, Roberts AW, et al. Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Blood. 2015;125(17):2649–2655.
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Odenike O, Singer JW, et al. Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. J Hematol Oncol. 2016;9:137.
   PubMed Web of Science ®Google Scholar
• Mesa RA, Vannucchi AM, Mead A, et al. Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial. Lancet Hematol. 2017;4(5):e225–e236.
   PubMed Web of Science ®Google Scholar
• Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis. A randomized clinical trial. JAMA Oncol. 2018;4(5):652–659.
   PubMed Web of Science ®Google Scholar
• Mascarenhas J, Virtgaym E, Stal M, et al. Outcomes of patients with myelofibrosis treated with compassionate use pacritinib: a sponsor-independent international study. Annals Hematol. 2018;97(8):1369–1374.
   PubMed Web of Science ®Google Scholar
• Gupta V, Mesa RA, Michael WN, et al. A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis. Haematologica. 2017;102:94–102.
   PubMed Web of Science ®Google Scholar
• Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: A phase III randomized trail of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol. 2017;35(34):3844–3850.
   PubMed Web of Science ®Google Scholar
• Harrison CN, Vannucchi A, Platzbecker U, et al. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018;5:e73–81.
   PubMed Web of Science ®Google Scholar
• Mascarenhas J, Hoffman R. Don’t Judge a JAK2 inhibitor by spleen response alone. Lancet Haematol. 2018;5:e56–57.
   PubMed Web of Science ®Google Scholar
• Pardanani A, Harrison CN, Cortes JE, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis: a randomized clinical trial. JAMA Oncol. 2015;1(5):643–651.
   PubMed Web of Science ®Google Scholar
• Harrison CN, Schaap N, Vannucchi AM, et al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017;4(7):e317–e324.
   PubMed Web of Science ®Google Scholar
• Curto-Garcia N, Harrison CN, McLornan DP, et al. Thiamine deficiency appears uncommon in patients with myeloproliferative neoplasms. Br J Hematol. 2017;178:338–340.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Zhang Y, Diamond S, et al. The Janus kinase 2 inhibitor fedratinib inhibits thiamine uptake: a putative mechanism for the onset of Wernicke’s encephalopathy. Drug Metab Dispos. 2014;42(10):1656–1662.
   PubMed Web of Science ®Google Scholar
• Hazell AS, Afadlal S, Cheresh DA, et al. Treatment of rats with the JAK-2 inhibitor fedratinib does not lead to experimental Wernicke’s encephalopathy. Neurosci Lett. 2017;642:163–167.
   PubMed Web of Science ®Google Scholar
• Kremyanskaya M, Mascarenhas J, Rampal R, et al. Development of extramedullary sites of leukemia during ruxolitinib treatment for myelofibrosis. Br J Haematol. 2014;167(1):144–146.
   PubMed Web of Science ®Google Scholar
• Newberry KJ, Patel K, Masarova L, et al. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017;130(9):1125–1131.
   PubMed Web of Science ®Google Scholar
• Foucar CE, Stein BL. Contemporary use of interferon therapy in the myeloproliferative neoplasms. Curr Hematol Malig Rep. 2017;12(5):406–414.
   PubMed Web of Science ®Google Scholar
• Silver RT, Barel AC, Lascu T, et al. The effect of initial molecular profile on response to recombinant interferon-α (rIFNα) treatment in early myelofibrosis. Cancer. 2017;123(14):2680–2687.
   PubMed Web of Science ®Google Scholar
• Ianotto JC, Boyer-Perrard F, Gyan E, et al. Efficacy and safety of pegylated-interferon α-2a in myelofibrosis: a study by the FIM and GEM French coopoerative groups. Br J Haematol. 2013;162:783–791.
   PubMed Web of Science ®Google Scholar
• Kroger N, Zabelina T, Alchalby H, et al. Dynamic of bone marrow fibrosis regression predicts survival after allogeneic stem cell transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2014;20:812–815.
   PubMed Web of Science ®Google Scholar
• Gupta V, Hari P, Hoffman R. Allogeneic hematopoietic cell transplantation for myelofibrosis in the era of JAK inhibitors. Blood. 2012;120(7):1367–1379.
   PubMed Web of Science ®Google Scholar
• Kroger N, Gioggino T, Scott BL, et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood. 2015;12(21):3347–3350.
   Google Scholar
• Guardiola P, Anderson JE, Bandini G, et al. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center collaborative study. Blood. 1999;93(9):2831–2838.
   PubMed Web of Science ®Google Scholar
• Deeg HJ, Gooley TA, Flowers ME, et al. Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Blood. 2003;102(12):3912–3918.
   PubMed Web of Science ®Google Scholar
• Kerbauy DM, Gooley TA, Sale GE, et al. Hematopoietic cell transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. Biol Blood Marrow Transplant. 2007;13(3):355–365.
   PubMed Web of Science ®Google Scholar
• Gupta V, Malone AK, Hari PN, et al. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2014;20:89–97.
   PubMedGoogle Scholar
• Kroger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2009;114(26):5264–5270.
   PubMed Web of Science ®Google Scholar
• Rondelli D, Goldberg JD, Isola L, et al. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2014;124(7):1183–1191.
   PubMed Web of Science ®Google Scholar
• Robin M, Porcher R, Wolschke C, et al. Outcome after transplantation according to reduced-intensity conditioning regimen in patients undergoing transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2016;22:1206–1211.
   PubMed Web of Science ®Google Scholar
• Gupta V, Kroger N, Aschan J, et al. A retrospective comparison of conventional intensity conditioning and reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in myelofibrosis. Bone Marrow Transplant. 2009;44(5):317–320.
   PubMed Web of Science ®Google Scholar
• Takagi S, Ota Y, Uchida N, et al. Successful engraftment after reducced-intensity umbilical cord blood transplantation for myelofibrosis. Blood. 2010;116(4):649–652.
   PubMed Web of Science ®Google Scholar
• Robin M, Giannotti F, Deconinck E, et al. Unrelated cord blood transplantation for patients with primary or secondary myelofibrosis. Biol Blood Marrow Transplant. 2014;20(11):1841–1846.
   PubMed Web of Science ®Google Scholar
• Bregante S, Dominietto A, Ghiso A, et al. Improved outcome of alternative donor transplantations in patients with myelofibrosis: from unrelated to haploidentical family donors. Biol Blood Marrow Transplant. 2016;22:324–329.
   PubMed Web of Science ®Google Scholar
• Keyzner A, Han S, Shapiro S, et al. Outcome of allogeneic hematopoietic stem cell transplantation for patients with chronic and advanced phase myelofibrosis. Biol Blood Marrow Transplant. 2016;22(2):2180–2186.
   PubMed Web of Science ®Google Scholar
• Lussana F, Rambaldi A, Finazzi MC, et al. Allogeneic hematopoietic stem cell transplantation in patients with polycythemia vera or essential thrombocythemia transformed to myelofibrosis or acute myeloid leukemia: a report from the MPN Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2014;99(5):916–921.
   PubMed Web of Science ®Google Scholar
• Alchalby H, Zabelina T, Stubig T, et al. Allogeneic stem cell transplantation for myelofibrosis with leukemic transformation: a study from the Myeloproliferative Neoplasm Subcommittee of the CMWP of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2014;20(2):279–281.
   PubMed Web of Science ®Google Scholar
• Scott BL, Gooley TA, Sorror ML, et al. The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood. 2012;119(11):2657.
   PubMed Web of Science ®Google Scholar
• Kroger N, Panagiota V, Badbaran A, et al. Impact of molecular genetics on outcome in myelofibrosis patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23:1095–1101.
   PubMed Web of Science ®Google Scholar
• McLornan DP, Szydlo R, Robin M, et al. Outcome of patients with Myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT. Br J Haematol. 2018;182(3):418–422.
   Web of Science ®Google Scholar
• Shah MV, Patel KP, Luthra R, et al. Sensitive PCR-based monitoring and early detection of relapsed JAK2 V617F myelofibrosis following transplantation. Br J Haematol. 2017. Epub.
   Google Scholar
• Lange T, Edelmann A, Sieboltz U, et al. JAK2 p.V617F allele burden in myeloproliferative neoplasms one month after allogeneic stem cell transplantation significantly predicts outcome and risk of relapse. Haematologica. 2013;98(5):722–728.
   PubMed Web of Science ®Google Scholar
• Haslam K, Langabeer SE. Monitoring minimal residual disease in the myeloproliferative neoplasms: current applications and emerging approaches. Biomed Res Int 2016;2016.
   Web of Science ®Google Scholar
• Kroger N, Alchalby H, Klyuchnikov E, et al. JAK2-V617F-triggered preemptive and salvage adoptive immunotherapy with donor-lymphocyte infusion in patients with myelofibrosis after allogeneic stem cell transplantation. Blood. 2009;113(8):1866–1868.
   PubMed Web of Science ®Google Scholar
• Klyuchnikov E, Holler E, Bornhauser M, et al. Donor lymphocyte infusions and second transplantation as salvage treatment for relapsed myelofibrosis after reduced-intensity allografting. Br J Haematol. 2012;159(2):172–181.
   PubMed Web of Science ®Google Scholar
• Alchalby H, Yunus DR, Zabelina T, et al. Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transplant. 2016;51(9):1223–1227.
   PubMed Web of Science ®Google Scholar
• Hart C, Klatt S, Barop J, et al. Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation. Haematologica. 2016;101(11):1407–1416.
   PubMed Web of Science ®Google Scholar
• Klyuchnikov E, El-Cheikh J, Sputteek A, et al. CD34(+)-selected stem cell boost without further conditioning for poor graft function after allogeneic stem cell transplantation in patients with hematological malignancies. Biol Blood Marrow Transplant. 2014;20(3):382–386.
   PubMed Web of Science ®Google Scholar
• Robin M, Zine M, Chevret S, et al. The Impact of splenectomy in myelofibrosis patients before allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23(6):958–964.
   PubMed Web of Science ®Google Scholar
• Schroeder MA, Choi J, Staser K, et al. The role of Janus kinase signaling in graft-versus-host disease and graft versus leukemia. Biol Blood Marrow Transplant. 2018;24(6):1125–1134.
   PubMed Web of Science ®Google Scholar
• Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29(10):2062–2068.
   PubMed Web of Science ®Google Scholar
• Kroger N, Shahnaz Syed Abd Kadir S, Zabelina T, et al. Peritransplantation ruxolitinib prevents acute graft-versus-host disease in patients with myelofibrosis undergoing allogenic stem cell transplantation. Biol Blood Marrow Transplant. 2018. Epub.
   Google Scholar
• Baron F, Ruggeri A, Nagler A. Methods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications. Expert Rev Hematol. 2016;9(3):297–314.
   PubMed Web of Science ®Google Scholar
• Mocellin S, Pooley KA, Nitti D. Telomerase and the search for the end of cancer. Trends Mol Med. 2013;19:125–133.
   PubMed Web of Science ®Google Scholar
• Vasko T, Kaifie A, Stope MB, et al. Telomeres and telomerase in hematopietic dysfunction: prognostic implications and pharmacolicgical intevantions. Int J Mol Sci. 2017;18:2267.
   Google Scholar
• Tefferi A, Lasho TL, Begna KH, et al. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Eng J Med. 2015;373(10):908–919.
   PubMed Web of Science ®Google Scholar
• Mosoyan G, Kraus T, Ye F, et al. Imetelstat, a telomerase inhibitor, differentially affects normal and malignant megakaryopoiesis. Leukemia. 2017;31:2458–2467.
   PubMed Web of Science ®Google Scholar
• Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067–1073.
   PubMed Web of Science ®Google Scholar
• Saenz DT, Fiskus W, Manshouri T, et al. BET protein bromodomain inhibitor-based combinations are highly active against post-myeloproliferative neoplasms secondary AML cells. Leukemia. 2017;31:678–687.
   PubMed Web of Science ®Google Scholar
• Kleppe M, Koche R, Zou L, et al. Dual targeting of oncogenic activation and inflammatory signaling increases therapeutic efficacy in myeloproliferative neoplasms. Cancer Cell. 2018;33:29–43.
   PubMed Web of Science ®Google Scholar
• Carrancio S, Markovics J, Wong P, 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(6):870–882.
   PubMed Web of Science ®Google Scholar
• Iancu-Rubin C, Mosoyan G, Wang J, et al. Stromal cell-mediated inhibition of erythropoiesis can be attenuated by Sotatercept (ACE-011), an activin receptor type II ligand trap. Exp Hematol. 2013;41(2):155–166.e17.
   PubMed Web of Science ®Google Scholar
• Suragani RN, Cadena SM, Cawley SM, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20:408–414.
   PubMed Web of Science ®Google Scholar
• Komrokji R, Garcia-Manero G, Ades L, et al. Sotatercept with long-term extension for the treatment of anemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Lancet Haematol. 2018;5(2):e63–72.
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Germing U, Gotze KS, et al. Luspatercept for the treatment of anemia 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(10):1338–1347.
   PubMed Web of Science ®Google Scholar
• Bose P, Daver N, Pemmaraju N, et al. Sotatercept (ACE-011) alone or in combination with ruxolitinib in patients (pts) with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF) and anemia. Am Hematol Assoc Annu Meet Exposition, Blood, Atlanta GA. 2017;130(1):634.
   Google Scholar
• Prokocimer M, Molchadsky A, Rotter V. Dysfunctional diversity of p53 proteins in adult acute myeloid lekemia: projections on diagnostic workup and therapy. Blood. 2017;130(6):699–712.
   PubMed Web of Science ®Google Scholar
• Li Q, Lozano G. Molecular pathways: targeting Mdm2 and Mdm4 in cancer therapy. Clin Cancer Res. 2013;19(1):34–41.
   PubMed Web of Science ®Google Scholar
• Marcellino B, Tripodi J, Lu M, et al. Advanced forms of the myeloproliferative neoplasms are associated with chromosomal abnormalities involving 1q and 12q: implicating MDM2 and MDM4 in disease progression. Am Soc Hematol Annu Meet Exposition, Blood, Atlanta. 2017;130:204.
   Google Scholar
• Nakatake M, Monte-Mor B, Debili N, et al. JAK2(V617F) negatively regulates p53 stabilization by enhancing MDM2 via La expression in myeloproliferative neoplasms. Oncogene. 2012;31(10):1323–1333.
   PubMed Web of Science ®Google Scholar
• Lu M, Wang X, Li Y, et al. Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-alpha 2a specifically targets JAK2V617F-positive polycythemia vera cells. Blood. 2012;120(15):3098–3105.
   PubMed Web of Science ®Google Scholar
• Lu M, Xia L, Li Y, et al. The orally bioavailable MDM2 antagonist RG7112 and pegylated interferon α 2a target JAK2V617F-positive progenitor and stem cells. Blood. 2014;124(5):771–779.
   PubMed Web of Science ®Google Scholar
• Mascarenhas J, Lu M, Virtgaym E, et al. Open label phase I study of single agent oral RG7388 (idasanutlin) in patients with polycythemia vera and essential thrombocythemia. Am Soc Hematol Annu Meet Exposition, Blood, Atlanta GA. 2017;130(1):254.
   Google Scholar
• Neuzillet C, Tijeras-Raballand A, Cohen R, et al. Targeting the TGFβ pathway for cancer therapy. Pharmacol Ther. 2015;147:22–31.
   PubMed Web of Science ®Google Scholar
• Wang JC, Chang TH, Goldberg A, et al. Quantitative analysis of growth factor production in the mechanism of fibrosis in agnogenic myeloid metaplasia. Exp Hematol. 2006;34(12):1617–1623.
   PubMed Web of Science ®Google Scholar
• Vannucchi AM, Bianchi L, Paoletti F, et al. A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-beta1 in the development of myelofibrosis. Blood. 2005;105(9):3493–3501.
   PubMed Web of Science ®Google Scholar
• Schmitt A, Drouin A, Masse JM, et al. Polymorphonuclear neutrophil and megakaryocyte mutual involvement in myelofibrosis pathogenesis. Leuk Lymphoma. 2002;43(4):719–724.
   PubMed Web of Science ®Google Scholar
• O’Connor-McCourt MD, Lenferink AE, Zwaagstra J, et al. Abstract 4688: AVID200: a novel computationally-designed TGF-beta trap promoting anti-tumor T cell activity. Washington DC: American Association for Cancer Research Annual Meeting; 2017.
   Google Scholar
• Thwaites M, Koropatnick J, Tremblay G, et al. AVID200: A novel TGF-b inhibitor for treatment of anemia associated with myelodysplastic syndromes. Am Soc Hematol Annu Meet Exposition, Blood, Atlanta GA. 2017;130(1):2532.
   Google Scholar
• Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(22):480–489.
   PubMedGoogle Scholar
• Batlevi CL, Matsuki E, Brentjens RJ, et al. Novel immunotherapies in lymphoid malignancies. Nat Rev. 2016;13:40.
   Google Scholar
• Choi DC, Tremblay D, Iancu-Rubin C, et al. Programmed cell death-1 pathway inhibition in myeloid malignancies: implications for myeloproliferative neoplasms. Ann Hematol. 2017;96:919–927.
   PubMed Web of Science ®Google Scholar
• Craig R, Tripp SR, Deininger M, et al. Programmed death ligand (PD-L1) expression is increased in spleens of myelofibrosis patients. US Can Acad. 2016. Abstract 1353.
   Google Scholar
• Prestipino A, Emhardt A, Aumann K, et al. Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Tansl Med. 2018;10:7729.
   Web of Science ®Google Scholar
• Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.
   PubMed Web of Science ®Google Scholar
• Bocchia M, Defina M, Aprile L, et al. Peptide vaccines for hematological malignancies: a missed promise? Int J Hematol. 2014;99(2):107–116.
   PubMed Web of Science ®Google Scholar
• Linette GP, Carreno BM. Neoantigen vaccines pass the immunogenicity test. Trends Mol Med. 2017;10:869–871.
   Google Scholar
• Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations in calreticulin in myeloproliferative neoplasms. N Eng J Med. 2013;369(25):2379–2390.
   PubMed Web of Science ®Google Scholar
• Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Eng J Med. 2013;369(25):2391–2405.
   PubMed Web of Science ®Google Scholar
• Holmstrom MO, Martinenaite E, Ahmad SM, et al. The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy. Leukemia. 2018;32:429–437.
   PubMed Web of Science ®Google Scholar
• Cimen Bozkus C, Finnigan JP, Mascarnhas J, et al. Immune checkpoint blockade enhances mutated calreticulin-induced T-Cell immunity in myeloproliferative neoplasms. Am Soc Hematol Annu Meet Exposition, Blood, Atlanta GA. 2017;130(1):384.
   Google Scholar
• Holmstrom MO, Hjortso MD, Ahmad SM. The JAK2V617F mutation is a target for specific T cells in the JAK2V617F-positive myeloproliferative neoplasms. Leukemia. 2017;31:495–948.
   PubMed Web of Science ®Google Scholar