Pamela J. Sung, MD, PhD A hallmark of acute myeloid leukemia (AML) is a maturation arrest of myeloid-committed hematopoietic cells, and the specific sensitivity of acute promyelocytic leukemia (APL) to retinoic acid was identified in the early 1980s. 1 This discovery paved the way for initial clinical trials using all-trans retinoic acid (ATRA) in APL, which demonstrated efficacy through promoting differentiation to mature myeloid phenotypes.
2-4 Findings from subsequent studies identified a novel fusion of the RARA gene as the molecular basis of this response. 5 This molecular vulnerability of APL has been exploited with dual differentiating therapy using ATRA and arsenic trioxide, leading to more than 95% of patients being cured from this once highly fatal disease without the use of traditional cytotoxic chemotherapy. 6 Although targeted therapies have revolutionized how we care for patients with AML, with significant improvements in both survival and quality of life, persistent challenges remain in developing treatments with durable responses in non-APL subtypes.
Recent research from our team at Roswell Park Comprehensive Cancer Center in Buffalo, New York, supports a rationale for expanding the use of differentiation therapy to patients with other aggressive leukemia subtypes. The advent of next-generation sequencing technologies has largely identified the molecular underpinnings of the non-APL subtypes of AML. Unfortunately, we have yet to see similar results with differ.
