Our laboratory studies the molecular pathogenesis of Chronic myelomonocytic leukemia (CMML) with the goal of identifying novel therapeutic vulnerabilities. CMML is a rare and lethal hematopoietic malignancy characterized by a characteristic classical monocytosis and a propensity to transform to Acute Myeloid Leukemia (AML). Interestingly, the majority of CMML patients present in a clinically asymptomatic state for periods of weeks to months before progressing to a lethal disease that clinically manifests via a heterogenous group of symptoms. There are no FDA approved therapies that have been demonstrated to alter the natural history of disease and the goal of our laboratory is to provide the preclinical evidence to increase the armamentarium available to clinicians treating this disease. Although our focus is centrally on CMML, our work aims to address questions in the field that can be more broadly applicable to other types of leukemias and cancers.