NIH R01 · 2024
JAK/STAT signaling in the pathogenesis of DNMT3A mutant T-ALL
ABSTRACT Like other cancers, T-cell acute lymphoblastic leukemia (T-ALL) arises from the accumulation of genetic abnormalities that impair function of immature T-cell progenitors. DNMT3A, which encodes a de novo DNA methyltransferase enzyme that catalyzes the establishment of new DNA methylation marks on the genome, is recurrently mutated in 10-18% of adult T-ALL cases and confers a poor clinical prognosis. We recently showed using genetic mouse models that Dnmt3a acts as a T-cell tumor suppressor. Introduction of an activating Notch1 mutation into a Dnmt3a loss-of-function genetic background (a common genetic combination in patients) generated a lethal T-ALL with half the latency period…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.