Chronic myelomonocytic leukemia: lost in classification?

Abstract

Chronic myelomonocytic leukemia (CMML) comprises a spectrum of disease variably considered as a myelodysplastic (MDS) and/or myeloproliferative (MPD) disorder. Now classified by the WHO within a separate nosological group from MDS or MPD, the reality is that there is a dynamic of evolution through increasing monocyte counts in one-third of patients. The principal clinical difference between CMML and other MPD is the presence of ineffective hematopoiesis, manifesting as more frequent anemia and thrombocytopenia in CMML. A fundamental biological characteristic shared with MPD is progenitor hypersensitivity to growth factors, but the pathways mediating this likely differ, as does the lineage specificity. Activation of the STAT pathway in MPD contrasts with frequent RAS pathway activation in CMML. Therapy of CMML is unsatisfactory, with the median age dictating that supportive care and control of myeloproliferation remains the mainstay for the majority. Intensive chemotherapy alone is of little benefit, and stem cell transplantation is the only curative modality in the small number of eligible patients, although outcome remains suboptimal. A deeper understanding of the biological basis of CMML may lead to targeted therapy analogous to the evolving management of MPD best exemplified for chronic myeloid leukemia.