Advertisement

Blastic Transformation of BCR-ABL-Negative Myeloproliferative Neoplasms

  • Madappa N. Kundranda
  • Raoul Tibes
  • Ruben A. Mesa
Chapter
Part of the Hematologic Malignancies book series (HEMATOLOGIC)

Abstract

The BCR-ABL-negative myeloproliferative neoplasms (MPNs) of essential thrombocythemia, polycythemia vera, and primary myelofibrosis have an increasing predisposition over the course of a patient’s illness to transform to overt acute leukemia what is referred to as MPN-Blast Phase (MPN-BP). Although the transformation of MPNs into acute leukemia is by itself a very rare phenomenon, once this has occurred, it is associated with poor response to chemotherapy and a high risk of relapse after allogeneic stem cell transplant (ASCT) and hence resulting in very poor survival in most cases. Pathogenetic mechanisms which lead to an MPN progressing to MPN-BP are incompletely understood but seem to correlate with accumulation of additional karyotypic abnormalities as opposed to increases in MPN-associated molecular lesion burden (such as JAK2 V617F). The development of MPN-BP is heralded by worsening cytopenias, constitutional symptoms, and a very poor survival despite therapeutic intervention. Risk factors for developing MPN-BP include both features at diagnosis (such as increased peripheral blood blasts, karyotypic abnormalities, and thrombocytopenia), as well as exposure to established agents which enhance leukemogenesis (i.e., P-32 and alkylators). Current therapies for the MPNs are limited, and no therapy other than an ASCT has clearly altered the natural history of these neoplasms. Therefore, an overall management plan that incorporates the possibility of ASCT should be developed for patients with MPN-BP at the time of diagnosis. However, it is not all dark and gray in the MPN-BP world; in last 6 years, we have made more advances in the treatment of MPNs than in the last 60 years. Multiple avenues of therapeutic investigation are ongoing to treat, or prevent, MPN-BP including early allogeneic stem cell transplantation, hypomethylating agents, and JAK2 inhibition.

Keywords

Acute Myeloid Leukemia JAK2 V617F JAK2 V617F Mutation Blast Phase Leukemic Transformation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

aCML

Atypical chronic myeloid leukemia

AML

Acute myeloid leukemia

ASCT

Allogeneic stem cell transplant

ASXL1

Additional sex combs-like 1

ATP

Adenosine triphosphate

CMML

Chronic myelomonocytic leukemia

CR

Complete response

ESA

Erythroid stimulating agent

ET

Essential thrombocythemia

HDAC

Histone deacetylase

HPI

Hedgehog pathway inhibitors

HSCT

Hematopoietic stem cell transplant

ICSBP

Interferon consensus sequence binding protein

IDH

Isocitrate dehydrogenase

IKZF1

IKAROS family zinc finger 1

IPSS

International Prognostic Scoring System

IWG-MRT

International Working Group for Myelofibrosis Research and Treatment

MPL

Myeloproliferative leukemia

MPN

Myeloproliferative neoplasm

MPN-BP

Myeloproliferative neoplasm blast phase

mTOR

Mammalian target of rapamycin

NHEJ

Nonhomologous end joining

Ph

Philadelphia (chromosome)

PMV

Primary myelofibrosis

PV

Polycythemia vera

ROS

Reactive oxygen species

SNP-A

Single nucleotide polymorphism analysis

WHO

World Health Organization

References

  1. Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296:1653–1655PubMedCrossRefGoogle Scholar
  2. Abdel-Wahab O, Pardanani A, Patel J et al (2011) Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia 25(7):1200–1202PubMedCrossRefGoogle Scholar
  3. Barosi G, Ambrosetti A, Centra A et al (1998) Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia. Blood 91:3630–3636PubMedGoogle Scholar
  4. Barosi G, Viarengo G, Pecci A et al (2001) Diagnostic and clinical relevance of the number of circulating CD34(+) cells in myelofibrosis with myeloid metaplasia. Blood 98:3249–3255PubMedCrossRefGoogle Scholar
  5. Baxter EJ, Scott LM, Campbell PJ et al (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061PubMedGoogle Scholar
  6. Beer PA, Delhommeau F, LeCouedic JP et al (2010) Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood 115:2891–2900PubMedCrossRefGoogle Scholar
  7. Bejar R, Levine R, Ebert BL (2011) Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol 29:504–515PubMedCrossRefGoogle Scholar
  8. Bogenberger JM, Hagelstrom RT, Gonzales I et al (2010) Synthetic lethal RNAi screening identified inhibition of Bcl-2 family members as sensitizers to 5-Azacytidine in myeloid cells. Late Breaking Abstract LB-128, AACR annual meeting, Washington, DCGoogle Scholar
  9. Boultwood J, Perry J, Zaman R et al (2010) High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression. Leukemia 24:1139–1145PubMedCrossRefGoogle Scholar
  10. Carbuccia N, Murati A, Trouplin V et al (2009) Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 23:2183–2186PubMedCrossRefGoogle Scholar
  11. Cervantes F (2007) Myelofibrosis: biology and treatment options. Eur J Haematol Suppl 79(68):13–17CrossRefGoogle Scholar
  12. Cervantes F, Pereira A, Esteve J et al (1997) Identification of ‘short-lived’ and ‘long-lived’ patients at presentation of idiopathic myelofibrosis. Br J Haematol 97:635–640PubMedCrossRefGoogle Scholar
  13. Cervantes F, Mesa R, Barosi G (2007) New and old treatment modalities in primary myelofibrosis. Cancer J 13:377–383PubMedCrossRefGoogle Scholar
  14. Cervantes F, Dupriez B, Pereira A et al (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113:2895–2901PubMedCrossRefGoogle Scholar
  15. Cervantes F (2001) Prognostic factors and current practice in treatment of myelofibrosis with myeloid metaplasia: an update anno 2000. Pathologie-biologie 49(2):148–152Google Scholar
  16. Dameshek W (1951) Some speculations on the myeloproliferative syndromes. Blood 6:372–375PubMedGoogle Scholar
  17. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744PubMedCrossRefGoogle Scholar
  18. Dingli D, Schwager SM et al (2006) Prognosis in transplant-eligible patients with agnogenic myeloid metaplasia: a simple CBC-based scoring system. Cancer 106(3):623–630Google Scholar
  19. Ding Y, Harada Y, Imagawa J et al (2009) AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 114:5201–5205PubMedCrossRefGoogle Scholar
  20. Dupriez B, Morel P et al (1996). Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system. Blood 88(3):1013–1018Google Scholar
  21. Eghtedar A, Verstovsek S, Cortes JE et al (2010) Phase II study of the JAK 2 inhibitor, INCB018424, in patients with refractory leukemias including post-myeloproliferative disorder (MPD) acute myeloid leukemia (sAML). Blood 116:abstract 509Google Scholar
  22. Finazzi G, Caruso V, Marchioli R et al (2005) Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood 105:2664–2670PubMedCrossRefGoogle Scholar
  23. Green A, Beer P (2010) Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 362:369–370PubMedCrossRefGoogle Scholar
  24. Gross S, Cairns RA, Minden MD et al (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207:339–344PubMedCrossRefGoogle Scholar
  25. Huang J, Li CY, Mesa RA et al (2008) Risk factors for leukemic transformation in patients with primary myelofibrosis. Cancer 112:2726–2732PubMedCrossRefGoogle Scholar
  26. Invernizzi R, Travaglino E, Benatti C et al (2006) Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia. Eur J Haematol 76:494–501PubMedCrossRefGoogle Scholar
  27. Jager R, Gisslinger H, Passamonti F et al (2010) Deletions of the transcription factor Ikaros in myeloproliferative neoplasms. Leukemia 24:1290–1298PubMedCrossRefGoogle Scholar
  28. James C, Ugo V, Le Couedic JP et al (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148PubMedCrossRefGoogle Scholar
  29. Karanas A, Silver RT (1968) Characteristics of the terminal phase of chronic granulocytic leukemia. Blood 32:445–459PubMedGoogle Scholar
  30. Kiladjian JJ, Rain JD, Bernard JF, Briere J, Chomienne C, Fenaux P (2006) Long-term incidence of hematological evolution in three French prospective studies of hydroxyurea and pipobroman in polycythemia vera and essential thrombocythemia. Semin Thromb Hemost 32:417–421PubMedCrossRefGoogle Scholar
  31. Kiladjian JJ, Cassinat B, Chevret S et al (2008) Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 112:3065–3072PubMedCrossRefGoogle Scholar
  32. Ko M, Huang Y, Jankowska AM et al (2010) Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468:839–843PubMedCrossRefGoogle Scholar
  33. Konieczna I, Horvath E, Wang H et al (2008) Constitutive activation of SHP2 in mice cooperates with ICSBP deficiency to accelerate progression to acute myeloid leukemia. J Clin Invest 118:853–867PubMedGoogle Scholar
  34. Kralovics R (2008) Genetic complexity of myeloproliferative neoplasms. Leukemia 22:1841–1848PubMedCrossRefGoogle Scholar
  35. Kralovics R, Passamonti F, Buser AS et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790PubMedCrossRefGoogle Scholar
  36. Kroger N, Zabelina T, Schieder H et al (2005) Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis. Br J Haematol 128:690–697PubMedCrossRefGoogle Scholar
  37. Levine RL, Wadleigh M, Cools J et al (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397PubMedCrossRefGoogle Scholar
  38. Lopes da Silva R, Ribeiro P, Lourenco A et al (2011) What is the role of JAK2 V617F mutation in leukemic transformation of myeloproliferative neoplasms? Lab Hematol 17:12–16PubMedCrossRefGoogle Scholar
  39. Lorusso PM, Rudin CM, Reddy JC (2011) Phase I trial of hedgehog pathway inhibitor GDC-0449 in patients with refractory, locally-advanced or metastatic solid tumors. Clin Cancer Res 17(8):2502–2511PubMedCrossRefGoogle Scholar
  40. Lu X, Levine R, Tong W et al (2005) Expression of a homodimeric type I cytokine receptor is required for JAK2 V617F-mediated transformation. Proc Natl Acad Sci USA 102:18962–18967PubMedCrossRefGoogle Scholar
  41. Makishima H, Jankowska AM et al (2011) CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia. Blood 117(21):198–206Google Scholar
  42. Mascarenhas J, Wang X, Rodriguez A et al (2009) A phase I study of LBH589, a novel histone deacetylase inhibitor in patients with primary myelofibrosis (PMF) and post-polycythemia/essential thrombocythemia myelofibrosis (Post-PV/ET MF). ASH annual meeting abstracts 114:308Google Scholar
  43. Mesa RA, Li CY, Ketterling RP et al (2005) Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood 105:973–977PubMedCrossRefGoogle Scholar
  44. Mesa RA, Nagorney DS, Schwager S et al (2006a) Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer 107:361–370PubMedCrossRefGoogle Scholar
  45. Mesa RA, Powell H, Lasho T et al (2006b) JAK2(V617F) and leukemic transformation in myelofibrosis with myeloid metaplasia. Leuk Res 30:1457–1460PubMedCrossRefGoogle Scholar
  46. Mesa RA, Cervantes F, Verstovsek S et al (2007a) Clinical evolution to primary myelofibrosis – blast phase: an international working group for myelofibrosis research and treatment (IWG-MRT) collaborative retrospective analysis. Blood 110:682Google Scholar
  47. Mesa RA, Verstovsek S, Cervantes F et al (2007b) Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT). Leuk Res 31:737–740PubMedCrossRefGoogle Scholar
  48. Mesa RA, Verstovsek S, Rivera C et al (2009) 5-Azacitidine has limited therapeutic activity in myelofibrosis. Leukemia 23:180–182PubMedCrossRefGoogle Scholar
  49. Najean Y, Rain JD (1997) Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood 90:3370–3377PubMedGoogle Scholar
  50. Osgood EE (1964) Contrasting incidence of acute monocytic and granulocytic leukemias in P32-treated patients with polycythemia vera and chronic lymphocytic leukemia. J Lab Clin Med 64:560–573PubMedGoogle Scholar
  51. Pancrazzi A, Guglielmelli P, Ponziani V et al (2008) A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction. J Mol Diagn 10:435–441PubMedCrossRefGoogle Scholar
  52. Pardanani A, Lasho T, Finke C et al (2010) LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 24:1713–1718PubMedCrossRefGoogle Scholar
  53. Parmentier C (2003) Use and risks of phosphorus-32 in the treatment of polycythaemia vera. Eur J Nucl Med Mol Imaging 30:1413–1417PubMedCrossRefGoogle Scholar
  54. Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812PubMedCrossRefGoogle Scholar
  55. Petti MC, Latagliata R, Spadea T et al (2002) Melphalan treatment in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 116:576–581PubMedCrossRefGoogle Scholar
  56. Pietra D, Li S, Brisci A et al (2008) Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 111:1686–1689PubMedCrossRefGoogle Scholar
  57. Pikman Y, Lee BH, Mercher T et al (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 3:e270PubMedCrossRefGoogle Scholar
  58. Quintas-Cardama A, Kantarjian H, Manshouri T et al (2009) Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 27:5418–5424PubMedCrossRefGoogle Scholar
  59. Rambaldi A, Dellacasa CM, Salmoiraghi S et al (2008) A phase 2A study of the histone-deacetylase inhibitor ITF2357 in patients with JAK2 V617F positive chronic myeloproliferative neoplasms. ASH annual meeting abstracts 112:100Google Scholar
  60. Saberwal G, Horvath E, Hu L et al (2009) The interferon consensus sequence binding protein (ICSBP/IRF8) activates transcription of the FANCF gene during myeloid differentiation. J Biol Chem 284:33242–33254PubMedCrossRefGoogle Scholar
  61. Sallmyr A, Fan J, Rassool FV (2008) Genomic instability in myeloid malignancies: increased reactive oxygen species (ROS), DNA double strand breaks (DSBs) and error-prone repair. Cancer Lett 270:1–9PubMedCrossRefGoogle Scholar
  62. Schaub FX, Looser R, Li S et al (2010) Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood 115:2003–2007PubMedCrossRefGoogle Scholar
  63. Scott BL, Deeg HJ (2010) Myelodysplastic syndromes. Annu Rev Med 61:345–358PubMedCrossRefGoogle Scholar
  64. Scott BL, Storer BE, Greene JE et al (2007a) Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia. Biol Blood Marrow Transplant 13:345–354PubMedCrossRefGoogle Scholar
  65. Scott LM, Tong W, Levine RL et al (2007b) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356:459–468PubMedCrossRefGoogle Scholar
  66. Silva M, Richard C, Benito A et al (1998) Expression of Bcl-x in erythroid precursors from patients with polycythemia vera. N Engl J Med 338:564–571PubMedCrossRefGoogle Scholar
  67. Steinberg MH, Barton F, Castro O et al (2003) Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA 289:1645–1651PubMedCrossRefGoogle Scholar
  68. Swierczek SI, Yoon D, Prchal JT (2007) Blast transformation in a patient with primary myelofibrosis initiated from JAK2 V617F progenitor. Blood 110:a4665Google Scholar
  69. Tahiliani M, Koh KP, Shen Y et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935PubMedCrossRefGoogle Scholar
  70. Tam CS, Nussenzveig RM, Popat U et al (2008) The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms. Blood 112:1628–1637PubMedCrossRefGoogle Scholar
  71. Tefferi A, Elliot MA (2000) Serious myeloproliferative reactions associated with the use of thalidomide in myelofibrosis with myeloid metaplasia. Blood 96:4007PubMedGoogle Scholar
  72. Tefferi A, Vainchenker W (2011) Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 29(5):573–582PubMedCrossRefGoogle Scholar
  73. Tefferi A, Barosi G, Mesa RA et al (2006a) International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood 108:1497–1503PubMedCrossRefGoogle Scholar
  74. Tefferi A, Cortes J, Verstovsek S et al (2006b) Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 108:1158–1164PubMedCrossRefGoogle Scholar
  75. Tefferi A, Gangat N, Wolanskyj AP et al (2008a) 20+ yr without leukemic or fibrotic transformation in essential thrombocythemia or polycythemia vera: predictors at diagnosis. Eur J Haematol 80:386–390PubMedCrossRefGoogle Scholar
  76. Tefferi A, Lasho TL, Huang J et al (2008b) Low JAK2 V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 22:756–761PubMedCrossRefGoogle Scholar
  77. Tefferi A, Pardanani A, Lim KH et al (2009a) TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 23:905–911PubMedCrossRefGoogle Scholar
  78. Tefferi A, Verstovsek S, Barosi G et al (2009b) Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 27:4563–4569PubMedCrossRefGoogle Scholar
  79. Tefferi A, Lasho TL, Abdel-Wahab O et al (2010) IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 24:1302–1309PubMedCrossRefGoogle Scholar
  80. Theocharides A, Boissinot M, Girodon F et al (2007) Leukemic blasts in transformed JAK2 V617F-positive myeloproliferative disorders are frequently negative for the JAK2 V617F mutation. Blood 110:375–379PubMedCrossRefGoogle Scholar
  81. Thepot S, Itzykson R, Seegers V et al (2010) Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood 116:3735–3742PubMedCrossRefGoogle Scholar
  82. Thoennissen NH, Krug UO, Lee DH et al (2010) Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms. Blood 115:2882–2890PubMedCrossRefGoogle Scholar
  83. Tibes R, Bogenberger J, Choudhary A et al (2009a) RNAi-based identification of novel sensitizers to 5-azacytidine in myeloid leukemias. Haematologica 94(Suppl 2):219, abstract 0536Google Scholar
  84. Tibes R, McDonagh KT, Lekakis L et al (2009b) Phase I study of the novel survivin and cdc2/CDK1 inhibitor terameprocol in patients with advanced leukemias. Blood (ASH annual meeting abstracts #1039)Google Scholar
  85. Tiedt R, Hao-Shen H, Sobas MA et al (2008) Ratio of mutant JAK2 V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood 111:3931–3940PubMedCrossRefGoogle Scholar
  86. Tolcher AW, Mita A, Lewis LD et al (2008) Phase I and pharmacokinetic study of YM155, a small-molecule inhibitor of survivin. J Clin Oncol 26:5198–5203PubMedCrossRefGoogle Scholar
  87. Vannucchi AM, Guglielmelli P, Lupo L et al (2010) A phase 1/2 study of RAD001, a mTOR inhibitor, in patients with myelofibrosis: final results. ASH annual meeting abstracts 116:314Google Scholar
  88. Vardiman JW, Thiele J et al (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114(5):937–951Google Scholar
  89. Vardiman JW, Brunning RD, Harris NL (2001) WHO histological classification of chronic myeloproliferative diseases. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) World health organization classification of tumors: tumours of the haematopoietic and lymphoid tissues. International Agency for Research on Cancer (IARC) Press, Lyon, pp 17–44Google Scholar
  90. Vardiman JW, Thiele J, Arber DA et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951PubMedCrossRefGoogle Scholar
  91. Vigil C, Cortes J, Kantarjian HM et al (2009) Hypo-methylating therapy for the treatment of acute erythroleukemia patients. ASH annual meeting abstracts 114:2069Google Scholar
  92. Von Hoff DD, LoRusso PM, Rudin CM et al (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361:1164–1172CrossRefGoogle Scholar
  93. Weller M, Felsberg J, Hartmann C et al (2009) Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network. J Clin Oncol 27:5743–5750PubMedCrossRefGoogle Scholar
  94. Wolanskyj AP, Schwager SM, McClure RF et al (2006) Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc 81:159–166PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Madappa N. Kundranda
    • 1
  • Raoul Tibes
    • 1
  • Ruben A. Mesa
    • 1
  1. 1.Division of Hematology and OncologyMayo ClinicScottsdaleUSA

Personalised recommendations