Federal Grant Award Summary

Pennsylvania State University's Penn State Milton S. Hershey Medical Center received a $623,949 Project Grant from the National Cancer Institute under the Cancer Biology Research program (CFDA 93.396) effective July 1, 2026, through June 30, 2031. The award funds fundamental research investigating the regulation of TAL1 (T-cell acute lymphoblastic leukemia 1), a transcription factor aberrantly activated in approximately 60% of T-cell acute lymphoblastic leukemia (T-ALL) cases. The research employs advanced molecular techniques, including SGRNA tiling library screening and immunoprecipitation liquid chromatography-mass spectrometry (IP-LC/MS), to identify critical functional domains and characterize how post-translational acetylation of TAL1 at lysine residues 221 and 222 dynamically regulates its function in leukemogenesis versus normal hematopoiesis.

The research deliverables include development of knock-in Jurkat cell lines and conditional knock-in mouse models with distinct acetylation profiles (TAL1K2R and TAL1K2Q variants) to elucidate mechanisms distinguishing leukemic transformation from normal T-cell differentiation. Preliminary data indicate that acetylated TAL1 promotes T-cell differentiation and blocks leukemogenesis in xenograft models, while unacetylated TAL1 mimics leukemic phenotypes. These findings are expected to provide comprehensive mechanistic understanding of TAL1 domain structure and acetylation-mediated regulation relevant to T-ALL pathogenesis, potentially informing therapeutic approaches targeting this high-risk leukemia subtype associated with poor prognosis and high relapse rates.