Cutting the cord from myelodysplastic syndromes: chronic myelomonocytic leukemia-specific biology and management strategies

Abstract

Purpose of review: Chronic myelomonocytic leukemia (CMML) is a troublesome hematologic malignancy characterized by peripheral blood monocytosis, marrow dysplasia, cytopenias, frequent extramedullary involvement by clonal cells, and a propensity for progression to acute myeloid leukemia. Although previously considered a subtype of the myelodysplastic syndromes (MDS), CMML is now recognized as a distinct entity with unique biologic and clinical features. This change has created a scientific and clinical research landscape that makes it difficult to discern CMML-specific validated conclusions versus speculative extrapolation from more general MDS data.

Recent findings: Here, we review recent biologic observations that support the current CMML WHO classification, such as the high frequency of SRSF2 and ASXL1 mutations compared with MDS and critical dependence of CMML cells on granulocyte-macrophage colony-stimulating factor signaling. In addition, we discuss CMML-specific prognostic tools and therapeutic results of agents developed for MDS in patients with CMML.

Summary: The present review focuses on evidence supporting CMML ontology and identifies key clinical differences in the management of CMML and that of MDS subtypes.