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The Classic Myeloproliferative Neoplasms: Chronic Myelogenous Leukemia, Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis

Ayalew Tefferi

DOI: 10.1036/ommbid.368

ABSTRACT

  • The classic myeloproliferative neoplasms, including chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are a phenotypically diverse category of malignancies that are derived from stem cells in the myeloid lineage.

  • The first genetic alteration recognized as a cause of myeloproliferative disease was the translocation that creates the BCR-ABL gene fusion. Recently, activating mutations in JAK2 and MPL have been found in the majority of BCR-ABL-negative myeloproliferative neoplasms. Recurrent mutations in these genes provide clinically useful diagnostic markers.

  • Implicated by mutational evidence, the JAK-STAT pathway is a rational target for drug development. A number of anti-JAK2 drugs have undergone preclinical testing, and some of these have been introduced into clinical trials.

INTRODUCTION

The 2008 World Health Organization (WHO) classification system considers five broad categories of myeloid malignancies: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), MDS/MPN overlap, and molecularly characterized MPN with eosinophilia1 (Table 78-1). AML is defined by the presence of either 20 percent or more bone marrow/peripheral blood myeloblasts (or promyelocytes in case of acute promyelocytic leukemia) or AML-specific cytogenetic abnormalities such as t(8;21)(q22;q22), t(15;17)(q22;q12) and inv(16)(p13q22). MDS and MPN are distinguished by the exclusive presence of erythroid and granulocyte dysplasia in the former and cytosis in the latter. In contrast, both features are present in MDS/MPN overlap. The category of MPNs is operationally subclassified into “classic” and “nonclassic” variants; the former constitutes the topic of this chapter and includes chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).

Table 78-1Classification of Myeloid Neoplasms Modified from the 2008 World Health Organization Classification Scheme
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Table 78-1 Classification of Myeloid Neoplasms Modified from the 2008 World Health Organization Classification Scheme

  1. Acute myeloid leukemia

  2. Myelodysplastic syndromes (MDS)

  3. Myeloproliferative neoplasms (MPN)

    • 3.1. Classic

      • 3.1.1. Chronic myelogenous leukemia

      • 3.1.2. Polycythemia vera

      • 3.1.3. Essential thrombocythemia

      • 3.1.4. Primary myelofibrosis

    • 3.2. Nonclassic

      • 3.2.1. Chronic neutrophilic leukemia

      • 3.2.2. Chronic eosinophilic leukemia, not otherwise categorized

      • 3.2.3. Hypereosinophilic syndrome

      • 3.2.4. Mast cell disease

      • 3.2.5. MPNs, unclassifiable

  4. MDS/MPN

    • 1. 4.1. Chronic myelomonocytic leukemia

    • 1. 4.2. Juvenile myelomonocytic leukemia

    • 1. 4.3. Atypical chronic myeloid leukemia

    • 1. 4.4. MDS/MPN, unclassifiable

  5. Molecularly characterized MPNs with eosinophilia

    • 1. 5.1. Myeloid neoplasms associated with PDGFRA rearrangement

    • 1. 5.2. Myeloid neoplasms associated with PDGFRB rearrangement

    • 1. 5.3. Myeloid neoplasms associated with FGFR1 rearrangement (8p11 myeloproliferative syndrome)

HISTORICAL PERSPECTIVE

In 1951, William Dameshek (1900–1969) grouped CML, PV, ET, and PMF, along with DiGuglielmo’s syndrome (erythroleukemia), under the rubric of “myeloproliferative disorders (MPDs).”20 Since then, erythroleukemia has been reclassified as AML, whereas the other four, as indicated above, are now referred to as the classic MPNs.

CML was first described by John Hughes Bennett (1812–1875) in 1845.21 Gustav Heuck (1854–1940) was the first to describe PMF, in 1879.22...

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