Our Research

Acute myeloid leukemia (AML) is an aggressive blood cancer that develops when healthy hematopoietic stem cells sequentially gain mutations that lead to uncontrolled cell growth. Studies have demonstrated that mutations occurring early in this process are acquired in ‘preleukemic’ stem cells years, and sometimes decades, prior to AML diagnosis. Interestingly, the genes that are most commonly mutated in preleukemic stem cells are the same as those seen in a condition called clonal hematopoiesis (CH), which affects nearly 20% of elderly individuals. Patients with CH are at a 10-fold increased risk of developing a hematologic malignancy, and thus CH represents a preleukemic state in some individuals. Importantly, for patients with CH who progress to leukemia, the presence of a higher proportion of preleukemic cells at the time of AML diagnosis portends a worse overall survival. Despite their importance in the pathogenesis and prognosis of AML, the process through which preleukemic cells transform into leukemia and how the length of the preleukemic phase affects AML biology is currently unknown.