Skip to main content
SpringerLink
Log in
Book cover

Myeloproliferative Neoplasms pp 131–145Cite as

Blastic Transformation of BCR-ABL-Negative Myeloproliferative Neoplasms

  • Chapter
  • First Online:

  • 1005 Accesses

Part of the book series: Hematologic Malignancies ((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.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

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

  • Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296:1653–1655

    Article  PubMed  CAS  Google Scholar 

  • 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):1200–1202

    Article  PubMed  CAS  Google Scholar 

  • 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 91:3630–3636

    PubMed  CAS  Google Scholar 

  • 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 98:3249–3255

    Article  PubMed  CAS  Google Scholar 

  • Baxter EJ, Scott LM, Campbell PJ et al (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061

    PubMed  CAS  Google Scholar 

  • Beer PA, Delhommeau F, LeCouedic JP et al (2010) Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood 115:2891–2900

    Article  PubMed  CAS  Google Scholar 

  • Bejar R, Levine R, Ebert BL (2011) Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol 29:504–515

    Article  PubMed  CAS  Google Scholar 

  • 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, DC

    Google Scholar 

  • 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 24:1139–1145

    Article  PubMed  CAS  Google Scholar 

  • Carbuccia N, Murati A, Trouplin V et al (2009) Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 23:2183–2186

    Article  PubMed  CAS  Google Scholar 

  • Cervantes F (2007) Myelofibrosis: biology and treatment options. Eur J Haematol Suppl 79(68):13–17

    Article  Google Scholar 

  • 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 97:635–640

    Article  PubMed  CAS  Google Scholar 

  • Cervantes F, Mesa R, Barosi G (2007) New and old treatment modalities in primary myelofibrosis. Cancer J 13:377–383

    Article  PubMed  CAS  Google Scholar 

  • 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 113:2895–2901

    Article  PubMed  CAS  Google Scholar 

  • Cervantes F (2001) Prognostic factors and current practice in treatment of myelofibrosis with myeloid metaplasia: an update anno 2000. Pathologie-biologie 49(2):148–152

    Google Scholar 

  • Dameshek W (1951) Some speculations on the myeloproliferative syndromes. Blood 6:372–375

    PubMed  CAS  Google Scholar 

  • Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744

    Article  PubMed  CAS  Google Scholar 

  • 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):623–630

    Google Scholar 

  • Ding Y, Harada Y, Imagawa J et al (2009) AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 114:5201–5205

    Article  PubMed  CAS  Google Scholar 

  • 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):1013–1018

    Google Scholar 

  • 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 509

    Google Scholar 

  • 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 105:2664–2670

    Article  PubMed  CAS  Google Scholar 

  • Green A, Beer P (2010) Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 362:369–370

    Article  PubMed  CAS  Google Scholar 

  • 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 207:339–344

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Li CY, Mesa RA et al (2008) Risk factors for leukemic transformation in patients with primary myelofibrosis. Cancer 112:2726–2732

    Article  PubMed  Google Scholar 

  • Invernizzi R, Travaglino E, Benatti C et al (2006) Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia. Eur J Haematol 76:494–501

    Article  PubMed  CAS  Google Scholar 

  • Jager R, Gisslinger H, Passamonti F et al (2010) Deletions of the transcription factor Ikaros in myeloproliferative neoplasms. Leukemia 24:1290–1298

    Article  PubMed  CAS  Google Scholar 

  • James C, Ugo V, Le Couedic JP et al (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148

    Article  PubMed  CAS  Google Scholar 

  • Karanas A, Silver RT (1968) Characteristics of the terminal phase of chronic granulocytic leukemia. Blood 32:445–459

    PubMed  CAS  Google Scholar 

  • 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 32:417–421

    Article  PubMed  CAS  Google Scholar 

  • 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 112:3065–3072

    Article  PubMed  CAS  Google Scholar 

  • Ko M, Huang Y, Jankowska AM et al (2010) Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 468:839–843

    Article  PubMed  CAS  Google Scholar 

  • 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 118:853–867

    PubMed  CAS  Google Scholar 

  • Kralovics R (2008) Genetic complexity of myeloproliferative neoplasms. Leukemia 22:1841–1848

    Article  PubMed  CAS  Google Scholar 

  • Kralovics R, Passamonti F, Buser AS et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790

    Article  PubMed  CAS  Google Scholar 

  • 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 128:690–697

    Article  PubMed  Google Scholar 

  • 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 7:387–397

    Article  PubMed  CAS  Google Scholar 

  • 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 17:12–16

    Article  PubMed  Google Scholar 

  • 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):2502–2511

    Article  PubMed  CAS  Google Scholar 

  • 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 102:18962–18967

    Article  PubMed  CAS  Google Scholar 

  • 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):198–206

    Google Scholar 

  • 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 114:308

    Google Scholar 

  • Mesa RA, Li CY, Ketterling RP et al (2005) Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood 105:973–977

    Article  PubMed  CAS  Google Scholar 

  • 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 107:361–370

    Article  PubMed  Google Scholar 

  • Mesa RA, Powell H, Lasho T et al (2006b) JAK2(V617F) and leukemic transformation in myelofibrosis with myeloid metaplasia. Leuk Res 30:1457–1460

    Article  PubMed  CAS  Google Scholar 

  • 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 110:682

    Google Scholar 

  • 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 31:737–740

    Article  PubMed  Google Scholar 

  • Mesa RA, Verstovsek S, Rivera C et al (2009) 5-Azacitidine has limited therapeutic activity in myelofibrosis. Leukemia 23:180–182

    Article  PubMed  CAS  Google Scholar 

  • 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 90:3370–3377

    PubMed  CAS  Google Scholar 

  • 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 64:560–573

    PubMed  CAS  Google Scholar 

  • 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 10:435–441

    Article  PubMed  CAS  Google Scholar 

  • 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 24:1713–1718

    Article  PubMed  CAS  Google Scholar 

  • Parmentier C (2003) Use and risks of phosphorus-32 in the treatment of polycythaemia vera. Eur J Nucl Med Mol Imaging 30:1413–1417

    Article  PubMed  CAS  Google Scholar 

  • Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321:1807–1812

    Article  PubMed  CAS  Google Scholar 

  • Petti MC, Latagliata R, Spadea T et al (2002) Melphalan treatment in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 116:576–581

    Article  PubMed  CAS  Google Scholar 

  • Pietra D, Li S, Brisci A et al (2008) Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 111:1686–1689

    Article  PubMed  CAS  Google Scholar 

  • Pikman Y, Lee BH, Mercher T et al (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 3:e270

    Article  PubMed  Google Scholar 

  • 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 27:5418–5424

    Article  PubMed  CAS  Google Scholar 

  • 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 112:100

    Google Scholar 

  • 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 284:33242–33254

    Article  PubMed  CAS  Google Scholar 

  • 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 270:1–9

    Article  PubMed  CAS  Google Scholar 

  • 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 115:2003–2007

    Article  PubMed  CAS  Google Scholar 

  • Scott BL, Deeg HJ (2010) Myelodysplastic syndromes. Annu Rev Med 61:345–358

    Article  PubMed  CAS  Google Scholar 

  • 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 13:345–354

    Article  PubMed  Google Scholar 

  • Scott LM, Tong W, Levine RL et al (2007b) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356:459–468

    Article  PubMed  CAS  Google Scholar 

  • 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 338:564–571

    Article  PubMed  CAS  Google Scholar 

  • 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 289:1645–1651

    Article  PubMed  CAS  Google Scholar 

  • Swierczek SI, Yoon D, Prchal JT (2007) Blast transformation in a patient with primary myelofibrosis initiated from JAK2 V617F progenitor. Blood 110:a4665

    Google Scholar 

  • Tahiliani M, Koh KP, Shen Y et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324:930–935

    Article  PubMed  CAS  Google Scholar 

  • Tam CS, Nussenzveig RM, Popat U et al (2008) The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms. Blood 112:1628–1637

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Elliot MA (2000) Serious myeloproliferative reactions associated with the use of thalidomide in myelofibrosis with myeloid metaplasia. Blood 96:4007

    PubMed  CAS  Google Scholar 

  • Tefferi A, Vainchenker W (2011) Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 29(5):573–582

    Article  PubMed  CAS  Google Scholar 

  • 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 108:1497–1503

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Cortes J, Verstovsek S et al (2006b) Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 108:1158–1164

    Article  PubMed  CAS  Google Scholar 

  • 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 80:386–390

    Article  PubMed  Google Scholar 

  • 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 22:756–761

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Pardanani A, Lim KH et al (2009a) TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 23:905–911

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Verstovsek S, Barosi G et al (2009b) Pomalidomide is active in the treatment of anemia associated with myelofibrosis. J Clin Oncol 27:4563–4569

    Article  PubMed  CAS  Google Scholar 

  • 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 24:1302–1309

    Article  PubMed  CAS  Google Scholar 

  • 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 110:375–379

    Article  PubMed  CAS  Google Scholar 

  • 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 116:3735–3742

    Article  PubMed  CAS  Google Scholar 

  • 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 115:2882–2890

    Article  PubMed  CAS  Google Scholar 

  • 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 0536

    Google Scholar 

  • 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 

  • 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 111:3931–3940

    Article  PubMed  CAS  Google Scholar 

  • 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 26:5198–5203

    Article  PubMed  CAS  Google Scholar 

  • 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 116:314

    Google Scholar 

  • 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):937–951

    Google Scholar 

  • 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 17–44

    Google Scholar 

  • 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 114:937–951

    Article  PubMed  CAS  Google Scholar 

  • Vigil C, Cortes J, Kantarjian HM et al (2009) Hypo-methylating therapy for the treatment of acute erythroleukemia patients. ASH annual meeting abstracts 114:2069

    Google Scholar 

  • Von Hoff DD, LoRusso PM, Rudin CM et al (2009) Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361:1164–1172

    Article  Google Scholar 

  • 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 27:5743–5750

    Article  PubMed  CAS  Google Scholar 

  • 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 81:159–166

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA

    Madappa N. Kundranda, Raoul Tibes & Ruben A. Mesa

Authors
  1. Madappa N. Kundranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raoul Tibes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruben A. Mesa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruben A. Mesa .

Editor information

Editors and Affiliations

  1. Div. Ematologia, Ospedali Riuniti di Bergamo, Largo Barozzi 1, Bergamo, 24128, Italy

    Tiziano Barbui

  2. Dept. Internal Medicine, Div. Hematology, Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Ayalew Tefferi

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Kundranda, M.N., Tibes, R., Mesa, R.A. (2012). Blastic Transformation of BCR-ABL-Negative Myeloproliferative Neoplasms. In: Barbui, T., Tefferi, A. (eds) Myeloproliferative Neoplasms. Hematologic Malignancies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-24989-1_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-24989-1_12

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-24988-4

  • Online ISBN: 978-3-642-24989-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation