Table 1.

2016 World Health Organization (WHO) recommended diagnostic criteria for chronic myelomonocytic leukemia (CMML)

Presence of persistent (>3 months) peripheral blood monocytosis > 1 x109/L, with monocytes constituting ≥10% of the white blood cell count differential. Not meeting WHO criteria for BCR-ABL1 driven chronic myeloid leukemia, essential thrombocythemia, polycythemia vera or primary myelofibrosis*. No evidence for PDGFRA or PDGFRB rearrangements, and the absence of FGFR1 rearrangements or the PCM1-JAK2 fusion in the context of concomitant eosinophilia**. < 20% blasts/blasts equivalent (promonocytes, monoblasts and myeloblasts) in the peripheral blood and bone marrow. Dysplasia in one or more myeloid cell lineages. If myelodysplasia is absent or minimal, the diagnosis of CMML may still be made if the other requirements are met and (see point 6) An acquired clonal cytogenetic or molecular genetic abnormality (TET2, ASXL1, SRSF2 and SETBP1) is present in hemopoietic cells***.

^*Myeloproliferative neoplasms (MPN) such as primary myelofibrosis and polycythemia vera can present with concurrent monocytosis. A previous documented history of MPN excludes a diagnosis of CMML. In addition, the presence of MPN like features in the bone marrow, or the presence of MPN-associated driver mutations, especially MPL and CALR make the diagnosis of CMML unlikely.

^**PDGFRA abnormalities most often involve the cryptic CHIC2 deletion at chromosome 4q12, resulting in the FIP1L1-PDGFRA fusion, commonly associated with peripheral blood eosinophilia and increased bone marrow mast cells.

PDGFRB abnormalities most often involve the ETV6-PDGFRB gene fusion with ~25 additional reported partners. This fusion is associated with peripheral blood monocytosis and concomitant eosinophilia.

FGFR1 rearrangements often result in an aggressive stem cell leukemia/lymphoma syndrome characterized by MPN, eosinophilia and the development of T cell-acute lymphoblastic leukemia (ALL).

The PCM1-JAK2 fusion usually results in eosinophilia with T-ALL or B-ALL.

^***While gene mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and SETBP1 (~15%) are common in CMML, they are not specific for the disease. TET2 and ASXL1 mutations can also be detected in patients with normal blood counts as a part of age related clonal hematopoiesis (clonal hematopoiesis of indeterminate potential).