Targeting the pyrimidine synthesis pathway for differentiation therapy of acute myelogenous leukemia

One of the key features of acute leukemia is the differentiation arrest at early progenitor stage of hematopoietic maturation. This has led to the search for therapeutic agents that can overcome this differentiation block to promote terminal differentiation. The first and most notable clinical success to date has been treatment with all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL), which accounts for 10% of acute myeloid leukemias (AML) (1).