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Sochacki AL, Fischer MA, Savona MR. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes. Onco Targets Ther. 2016;9:2273-86doi: 10.2147/OTT.S83868.
Sochacki, A. L., Fischer, M. A., & Savona, M. R. (2016). Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes. OncoTargets and therapy, 92273-86. https://doi.org/10.2147/OTT.S83868
Sochacki, Andrew L, et al. "Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes." OncoTargets and therapy vol. 9 (2016): 2273-86. doi: https://doi.org/10.2147/OTT.S83868
Sochacki AL, Fischer MA, Savona MR. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes. Onco Targets Ther. 2016 Apr 15;9:2273-86. doi: 10.2147/OTT.S83868. eCollection 2016. PMID: 27143923; PMCID: PMC4844455.
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Onco Targets Ther. 2016 Apr 15;9:2273-86. doi: 10.2147/OTT.S83868. eCollection 2016.

Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes.

OncoTargets and therapy

Andrew L Sochacki, Melissa A Fischer, Michael R Savona

Affiliations

  1. Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  2. Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.

PMID: 27143923 PMCID: PMC4844455 DOI: 10.2147/OTT.S83868

Abstract

The discovery of JAK2 (V617F) a decade ago led to optimism for a rapidly developing treatment revolution in Ph(-) myeloproliferative neoplasms. Unlike BCR-ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) syndromes. JAK-STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK-STAT, hedgehog, PI3K-Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease.

Keywords: MDS/MPN neoplasms; emerging therapy

References

  1. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15825-30 - PubMed
  2. Br J Haematol. 2015 May;169(4):534-43 - PubMed
  3. Am J Hematol. 2012 Jan;87(1):66-8 - PubMed
  4. Curr Opin Hematol. 2013 Mar;20(2):169-75 - PubMed
  5. Blood Cancer J. 2015 Jul 17;5:e325 - PubMed
  6. Blood. 2011 Oct 6;118(14 ):3932-41 - PubMed
  7. Oncotarget. 2011 Jun;2(6):485-90 - PubMed
  8. N Engl J Med. 2013 Dec 19;369(25):2379-90 - PubMed
  9. Blood Cancer J. 2015 Aug 07;5:e335 - PubMed
  10. N Engl J Med. 2012 Mar 1;366(9):787-98 - PubMed
  11. Cancer Cell. 2005 Apr;7(4):387-97 - PubMed
  12. N Engl J Med. 2010 Sep 16;363(12):1117-27 - PubMed
  13. Blood. 2014 Aug 14;124(7):1062-9 - PubMed
  14. Leukemia. 2013 Jun;27(6):1322-7 - PubMed
  15. J Clin Oncol. 2010 Apr 10;28(11):1856-62 - PubMed
  16. Blood. 2001 Mar 15;97(6):1896 - PubMed
  17. Cancer Gene Ther. 2015 Mar;22(2):63 - PubMed
  18. Blood. 2006 Oct 1;108(7):2173-81 - PubMed
  19. Biol Blood Marrow Transplant. 2016 Feb;22(2):324-9 - PubMed
  20. Mayo Clin Proc. 2011 Dec;86(12):1188-91 - PubMed
  21. Br J Haematol. 2013 Apr;161(1):68-75 - PubMed
  22. Blood. 2012 Aug 16;120(7):1367-79 - PubMed
  23. Leukemia. 2010 Oct;24(10 ):1799-804 - PubMed
  24. Br J Haematol. 2008 Mar;140(6):610-24 - PubMed
  25. Leuk Lymphoma. 2014 Jan;55(1):121-7 - PubMed
  26. Br J Haematol. 2011 Feb;152(3):331-9 - PubMed
  27. Blood. 2000 Jun 1;95(11):3589-93 - PubMed
  28. Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18962-7 - PubMed
  29. Clin Cancer Res. 2013 May 15;19(10):2766-74 - PubMed
  30. Blood. 2005 Nov 15;106(10):3374-6 - PubMed
  31. Blood. 2015 Aug 6;126(6):790-7 - PubMed
  32. Leukemia. 2013 Jul;27(7):1504-10 - PubMed
  33. Blood. 2007 Aug 15;110(4):1092-7 - PubMed
  34. Blood. 2015 Mar 19;125(12):1857-65 - PubMed
  35. Leuk Lymphoma. 2008 Dec;49(12):2321-7 - PubMed
  36. Ann Hematol. 2010 Dec;89(12):1233-7 - PubMed
  37. Blood. 2009 Aug 27;114(9):1859-63 - PubMed
  38. N Engl J Med. 2013 Dec 19;369(25):2391-405 - PubMed
  39. Am J Hematol. 2008 May;83(5):363-5 - PubMed
  40. Blood. 2009 Mar 26;113(13):2895-901 - PubMed
  41. Leukemia. 2011 Jul;25(7):1217-9 - PubMed
  42. Blood. 2010 Mar 11;115(10 ):1969-75 - PubMed
  43. Br J Haematol. 2015 Apr;169(1):77-80 - PubMed
  44. Leukemia. 2013 Sep;27(9):1861-9 - PubMed
  45. Leuk Lymphoma. 2015 Jul;56(7):2092-7 - PubMed
  46. Blood. 2003 Apr 1;101(7):2534-41 - PubMed
  47. Leukemia. 2014 Aug;28(8):1736-8 - PubMed
  48. Blood. 2009 Jul 30;114(5):937-51 - PubMed
  49. Am J Hematol. 2011 Jan;86(1):96-8 - PubMed
  50. Blood. 2015 May 28;125(22):3393-400 - PubMed
  51. Cancer. 2003 Jul 1;98(1):100-9 - PubMed
  52. Curr Cancer Drug Targets. 2005 Sep;5(6):445-55 - PubMed
  53. Blood. 2010 Nov 25;116(22):4436-8 - PubMed
  54. Blood. 2010 Apr 15;115(15):3109-17 - PubMed
  55. J Clin Oncol. 2011 Feb 10;29(5):573-82 - PubMed
  56. Blood. 2010 Jun 24;115(25):5232-40 - PubMed
  57. J Clin Oncol. 2011 Mar 1;29(7):789-96 - PubMed
  58. Leuk Res. 2010 Aug;34(8):969-73 - PubMed
  59. Br J Haematol. 2005 Jun;129(6):771-5 - PubMed
  60. J Hematol Oncol. 2013 Oct 29;6(1):81 - PubMed
  61. Nagoya J Med Sci. 2015 Feb;77(1-2):7-17 - PubMed
  62. Pharmacol Ther. 2015 Jul;151:41-9 - PubMed
  63. Blood. 2012 Feb 2;119(5):1208-13 - PubMed
  64. Clin Cancer Res. 2010 Jan 1;16(1):338-47 - PubMed
  65. Nat Genet. 2001 Dec;29(4):465-8 - PubMed
  66. N Engl J Med. 2010 Aug 19;363(8):711-23 - PubMed
  67. Blood. 2013 Sep 5;122(10):1707-11 - PubMed
  68. Leukemia. 2014 Jul;28(7):1568-70 - PubMed
  69. Haematologica. 2015 Aug;100(8):1058-63 - PubMed
  70. Nat Genet. 2013 Aug;45(8):937-41 - PubMed
  71. Blood. 2009 Dec 17;114(26):5264-70 - PubMed
  72. Hematology Am Soc Hematol Educ Program. 2005;:195-200 - PubMed
  73. Lancet Haematol. 2015 Aug;2(8):e339-46 - PubMed
  74. Haematologica. 2013 Jan;98(1):107-13 - PubMed
  75. Clin Cancer Res. 2016 Aug 1;22(15):3746-54 - PubMed
  76. Science. 1995 Nov 3;270(5237):800-2 - PubMed
  77. Leukemia. 2013 Sep;27(9):1826-31 - PubMed
  78. Cancer Res. 2013 Feb 1;73(3):1076-85 - PubMed
  79. Cancer Res. 2011 Apr 15;71(8):2901-15 - PubMed
  80. N Engl J Med. 2015 Feb 12;372(7):601-12 - PubMed
  81. Nat Genet. 2013 Jan;45(1):18-24 - PubMed
  82. Blood. 2013 Apr 11;121(15):3005-15 - PubMed
  83. Am J Clin Pathol. 2009 Aug;132(2):281-9 - PubMed
  84. Blood. 2010 Oct 14;116(15):2857-8 - PubMed
  85. Blood. 2014 Oct 16;124(16):2487-97 - PubMed
  86. J Natl Cancer Inst. 2008 Feb 6;100(3):184-98 - PubMed
  87. J Clin Oncol. 2010 Dec 20;28(36):5321-6 - PubMed
  88. Leukemia. 2008 May;22(5):965-70 - PubMed
  89. J Clin Oncol. 2013 Jul 1;31(19):2428-36 - PubMed
  90. Am J Physiol Lung Cell Mol Physiol. 2013 Aug 1;305(3):L229-39 - PubMed
  91. Ann R Coll Surg Engl. 2015 Jul;97(5):345-8 - PubMed
  92. Blood. 2012 Mar 8;119(10):2196-204 - PubMed
  93. Blood. 2005 Feb 1;105(3):973-7 - PubMed
  94. Cancer. 2006 Jul 15;107(2):361-70 - PubMed
  95. J Clin Oncol. 2009 Oct 1;27(28):4760-6 - PubMed
  96. Leuk Res. 2015 May;39(5):501-4 - PubMed
  97. N Engl J Med. 2012 Mar 1;366(9):799-807 - PubMed
  98. Blood. 2008 Jul 1;112(1):141-9 - PubMed
  99. Nat Rev Cancer. 2015 Apr;15(4):201-15 - PubMed
  100. Blood. 2015 Apr 23;125(17 ):2649-55 - PubMed
  101. Cancer. 2006 May 1;106(9):1974-84 - PubMed
  102. Science. 2009 Jun 12;324(5933):1457-61 - PubMed
  103. Br J Haematol. 2013 Aug;162(3):326-35 - PubMed
  104. Nat Genet. 2013 Aug;45(8):942-6 - PubMed
  105. N Engl J Med. 2015 Sep 3;373(10):908-19 - PubMed
  106. Nat Genet. 2010 Aug;42(8):722-6 - PubMed
  107. Blood. 2012 Oct 11;120(15):3080-8 - PubMed
  108. Hematology Am Soc Hematol Educ Program. 2013;2013:538-44 - PubMed
  109. Nature. 2005 Apr 28;434(7037):1144-8 - PubMed
  110. J Clin Invest. 2008 Oct;118(10):3263-5 - PubMed
  111. Blood. 2015 May 21;125(21):3347-50; quiz 3364 - PubMed
  112. Oncogene. 2007 Oct 15;26(47):6724-37 - PubMed
  113. Blood Cancer J. 2015 Jul 31;5:e333 - PubMed
  114. Bone Marrow Transplant. 2014 Feb;49(2):179-84 - PubMed
  115. Nat Rev Cancer. 2003 Dec;3(12):903-11 - PubMed
  116. Blood. 2009 Jun 18;113(25):6403-10 - PubMed
  117. Haematologica. 2015 Sep;100(9):1117-30 - PubMed
  118. Leukemia. 2012 Mar;26(3):542-5 - PubMed
  119. Blood. 2014 Oct 9;124(15):2465-6 - PubMed
  120. Leukemia. 2014 Jul;28(7):1494-500 - PubMed
  121. Drug Metab Dispos. 2014 Oct;42(10):1656-62 - PubMed
  122. Arch Intern Med. 1982 Aug;142(8):1533-7 - PubMed
  123. Blood. 2005 Aug 15;106(4):1207-9 - PubMed
  124. Nat Rev Drug Discov. 2015 Oct;14(10):693-720 - PubMed
  125. Br J Haematol. 2010 Jul;150(1):83-7 - PubMed
  126. Br J Haematol. 1998 Aug;102(3):684-90 - PubMed
  127. Am J Hematol. 2012 Feb;87(2):204-6 - PubMed
  128. Leukemia. 2013 Oct;27(10):2100-2 - PubMed
  129. Blood. 2014 Jun 12;123(24):3714-9 - PubMed
  130. Blood. 2011 Apr 28;117(17):4552-60 - PubMed
  131. Blood. 2003 Dec 1;102(12):3912-8 - PubMed
  132. Leuk Lymphoma. 2013 Jul;54(7):1552 - PubMed
  133. Haematologica. 2014 Jan;99(1):e5-7 - PubMed
  134. Semin Cell Dev Biol. 2008 Aug;19(4):385-93 - PubMed

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