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1Division of Clinical Immunology & Rheumatology, Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA 2CAMBAC (Comprehensive Arthritis, Musculoskeletal, Bone and Autoimmunity Center), University of Alabama at Birmingham, Birmingham, CA, USA 3Division of Rheumatology, Allergy, and Immunology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, San Diego, CA, USA 4Department of Cellular and Molecular Medicine, University of California,...
Abstract T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism.
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