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INTRODUCTION

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Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells that manifest clinically as overproduction of cells that contribute to the myeloid lineage

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Classification WHO Myeloproliferative Neoplasm (MPN) Categories

  1. Classic MPN

    • Chronic myelogenous leukemia (CML); see Chapter 21

    • Polycythemia vera (PV)

    • Essential thrombocythemia (ET)

    • Primary myelofibrosis (PMF)

  2. "Nonclassic" MPNs

    • Chronic neutrophilic leukemia (CNL)

    • Mast cell disease (MCD)

    • Chronic eosinophilic leukemia not otherwise categorized (CEL-NOC)

    • "MPN unclassifiable"

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Epidemiology

BCR-ABL–negative classic MPN

Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)

Polycythemia vera (PV)

  1. Incidence: 0.8–2.6/100,000

  2. Median age at diagnosis: ≈60 years

  3. Median survival: >15 years

  4. 10-year risk of myelofibrosis: <4%

  5. 10-year risk of AML: <2%

 

Note: Longer disease duration and evolution into myelofibrosis significantly increase the risk of leukemic transformation

 

Ania BJ et al. Am J Hematol 1994;47:89–93

Gangat N et al. Br J Haematol 2007;138:354–358

Gangat N et al. Leukemia 2007;21:270–276

Mesa RA et al. Am J Hematol 1999;61:10–15

 

Essential thrombocythemia (ET)

  1. Incidence: 0.2–2.5/100,000

  2. Median age at diagnosis: ≈60 years

  3. Median survival: >15 years

  4. 10-year risk of myelofibrosis: ≈10%

  5. 10-year risk of AML: ≈6%

 

Note: Longer disease duration and evolution into myelofibrosis significantly increase the risk of leukemic transformation

Primary myelofibrosis (PMF)

  1. Incidence: 0.4–1.5/100,000

  2. Median age at diagnosis: ≈60 years

  3. Median survival: <3 years to >10 years

  4. 10-year risk of myelofibrosis: N/A

  5. 10-year risk of AML: ≈20% based on the presence or absence of well-defined prognostic determinants

  6. Most important indicators of adverse prognosis:

    • Age >65 years

    • Hemoglobin <10 g/dL

    • Leukocyte count >25,000/mm3

    • Circulating blasts ≥1%

    • Constitutional symptoms

    • Unfavorable karyotype included complex karyotype or single or two abnormalities including +8, −7/7q-, i(17q), −5/5q-, 12p-, inv(3), or 11q23 rearrangement

    • Thrombocytopenia <100,000/mm3

 

Cervantes F et al. Br J Haematol 1997;97:635–640

Dupriez B et al. Blood 1996;88:1013–1018

Gangat N et al. J Clin Oncol 2011;29:392–397

Passamonti F et al. Blood 2010;115:1703–1708

Tefferi A et al. Cancer 2007;109:2083–2088

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Mutations in MPN

Chronology:

  • 1951: CML, PV, ET, and PMF recognized to have significant overlap in both clinical and biological features and felt to be related diseases

  • 1960: CML recognized as distinct entity after discovery of Philadelphia chromosome

  • Early 1980s: Analysis of X chromosome inactivation patterns in women with CML, PV, ET, or PMF carrying a polymorphic variant of the glucose-6-phosphate dehydrogenase gene establishes all 4 diseases as clonal stem-cell disorders

  • 2005: Somatic mutation involving Janus Kinase 2 (JAK2) identified in patients with PV, ET, and PMF. Mutation at codon 617, [JAK2V617F] is a G→T transversion at nucleotide 1849 in exon 14 of JAK2 gene, with substitution of valine by phenylalanine at codon 617

  • 2006–2007: Additional JAK2 and MPL (thrombopoietin receptor) mutations described in these diseases; some induce PV-like (JAK2) or PMF-like (MPL) phenotype in mice

 

Adamson JW et al. N Engl J Med 1976;295:913–916

Dameshek W. Blood 1951;6:372–375

Fialkow PJ et al. Blood 1981;58:916–919

 

Mutations

  1. JAK2V617F mutations: 20–95%

    (Most frequent mutation in BCR-ABL-negative chronic ...

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