Novel therapeutic targets for chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a rare, age-related myeloid neoplasm with overlapping features of myelodysplastic syndromes/myeloproliferative neoplasms. Although gene mutations involving TET2, ASXL1 and SRSF2 are common, there are no specific molecular alterations that define the disease. Allogeneic stem cell transplant is the only curative option, with most patients not qualifying, due to advanced age at diagnosis and comorbidities. The only approved treatment options are hypomethylating agents; drugs that fail to alter the disease course or affect mutant allele burdens. Clinically CMML can be sub-classified into proliferative (pCMML) and dysplastic (dCMML) subtypes, with pCMML being associated with signaling mutations, myeloproliferative features, and a shorter overall survival. Given the paucity of effective treatment strategies there is a need for rationally informed and biomarker driven studies. This report will discuss current and prospective therapies for CMML and discuss the role for personalized therapeutics.