Damon Runyon Researchers

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Wallace A. Bourgeois, MD

Acute myeloid leukemia (AML) is an aggressive blood cancer that affects children and adults. One particularly difficult-to-treat subtype of AML that represents about 10% of all cases is characterized by a mutation in the KMT2A gene. Menin inhibitors (MI), a novel targeted therapy, have shown promise against this subtype in early clinical trials. Studies have also shown that compounds that degrade a protein called Ikaros can dramatically enhance the efficacy of MI. In seeking to uncover why MI and Ikaros protein degraders work well together, Dr. Bourgeois and his colleagues have found that both drugs target gene expression programs that are critical for the survival of KMT2A-mutant AML cells. Dr. Bourgeois is now working to better understand which genes can be targeted to further enhance the efficacy of Ikaros protein degraders in KMT2A-mutant AML. This work will shed light on the essential gene expression programs required for KMT2A-mutant AML cell survival, and ideally help guide drug development that specifically targets this subtype.

Project title: "Targeting JMJD1C and IKZF1 as therapeutic opportunities in KMT2A-rearranged leukemia"
Institution: Dana-Farber Cancer Institute
Award Program: Physician-Scientist
Sponsor(s) / Mentor(s): Scott A. Armstrong, MD, PhD
Cancer Type: Blood
Research Area: Epigenetics