Federal Grant Award Summary

The National Cancer Institute (NCI) awarded The University of Texas MD Anderson Cancer Center a $473,372 Project Grant under the Cancer Biology Research program (CFDA 93.396) to investigate proline tRNA (transfer RNA) biogenesis as an oncogenic driver and therapeutic target in T cell acute lymphoblastic leukemia (T-ALL). The research, which commenced April 8, 2026, and extends through March 31, 2031, will characterize the molecular mechanisms by which upregulated proline tRNA biogenesis promotes oncogenic gene expression programs in T-ALL and determine the in vivo oncogenic role of this pathway. Preliminary studies demonstrate that expression of the bifunctional enzyme glutamyl-prolyl-tRNA synthetase (EPRS1) and proline tRNA isoacceptors are significantly elevated in primary T-ALL samples compared to healthy controls, and that pharmacological inhibition of EPRS1's prolyl-tRNA synthetase activity induces cell death in T-ALL cells while sparing healthy donor T cells.

This research will generate mechanistic insights into tRNA deregulation in cancer progression and identify novel therapeutic vulnerabilities in T-ALL, addressing a critical gap in understanding the link between tRNA dysfunction and tumor pathogenesis. The deliverables will include molecular and proteomic analyses defining how deregulated proline tRNA biogenesis supports oncogenic protein synthesis, in vitro and in vivo experimental findings validating this pathway as a therapeutic target, and a scientific framework to support future drug development efforts targeting proline tRNA biogenesis in T-ALL and potentially other malignancies.