Modern classification, diagnostic criteria, and practical algorithms in myeloproliferative disorders

William Dameshek (1900-1969) is credited for introducing the term myeloproliferative disorders (MPDs) as well as the first classification scheme in MPDs; he nominated chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) as the original members of the group (1). These four classic MPDs are now part of a broader category of “chronic myeloid neoplasms,” which also includes the myelodysplastic syndrome (MDS) and the operationally named “nonclassic” MPDs (Table 1) (2,3). The latter include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), hypereosinophilic syndrome (HES), systemic mastocytosis (SM), the 8p11 myeloproliferative syndrome (EMS, a.k.a. stem cell leukemia and lymphoma syndrome), chronic basophilic leukemia, atypical CML (aCML), and “MPD not otherwise classified” (MPD-NOC) (Table 1). The World Health Organization (WHO) classification system for chronic myeloid neoplasms is different from that depicted in Table 1; the WHO system includes four subgroups of chronic myeloid neoplasms: MDS, MPD, MDS/MPD, and SM (4). The WHO MPD category includes the four classic MPDs as well as CNL, CEL, HES, and “MPD, unclassifiable.” The WHO MDS/MPD category includes Table 1 Modern Classification of Chronic Myeloid Neoplasms Main categories Subcategories Molecular signatures Myelodysplastic syndrome According to WHO classification system Classic myeloproliferative disorders 1. Chronic myeloid leukemia 100% BCR-ABL(+) 2. Polycythemia vera ∼95% JAK2V617F(+) ∼4% JAK2 exon 12 mutations(+) 3. Essential thrombocythemia ∼50% JAK2V617F(+) ∼1% MPLW515L/K(+) 4. Primary myelofibrosis ∼50% JAK2V617F(+) ∼5% MPLW515L/K(+) Nonclassic myeloproliferative disorders 1. Chronic myelomonocytic leukemia ∼3% JAK2V617F(+) 2. Juvenile myelomonocytic leukemia ∼30% PTPN11 mutation(+) ∼15% NF1 mutation(+) ∼15% RAS mutation(+) 3. Chronic neutrophilic leukemia ∼20% JAK2V617F(+) 4. Chronic eosinophilic leukemia ∼100% FIP1L1-PDGFRA(+) i. PDGFRA-rearranged 100% various PDGFRB translocationsii. PDGFRB-rearranged iii. Molecularly undefined 5. Hypereosinophilic syndrome 6. Systemic mastocytosis ∼90% KITD816V(+) i. KIT-mutated ii. Molecularly undefined 7. 8p11 Myeloproliferative syndrome 100% various FGFR1 translocations 8. Chronic basophilic leukemia 9. Atypical chronic myeloid leukemia ∼20% JAK2V617F(+) MPD not otherwise classified (MPD-NOC); includes the WHO categories of “MPD, unclassifiable,” “MDS/MPD, unclassifiable,” and “RARS-T” ∼20-50% JAK2V617F(+) Practical CMML, JMML, aCML, and “MDS/MPD, unclassifiable.” In the classification scheme outlined in Table 1, both MPD, unclassifiable, and MDS/MPD, unclassifiable, are listed under “MPD-NOC.”