Abstract 1679: Understanding the mechanism of Daple-PDGFRB gene fusion in leukemia

Abstract Gene fusion between the scaffolding protein Daple and cell-surface receptor PDGFRB have been identified in several patients with leukemia. Patients with Daple-PDGFRB gene fusion are responsive to tyrosine kinase inhibitors, suggesting that the kinase domain on the receptor is active. How the Daple-PDGFRB gene fusion is activated and affects leukemia cells is poorly understood. It is hypothesized that the PDGFRB kinase domains found in gene fusion remain constitutively active, leading to hyperactivation of cell-signaling downstream of receptor tyrosine kinases (RTKs). To test this, identified Daple-PDGFRB mutants found in patients were ectopically expressed in cells and kinase activation were determined using a phospho-specific antibody. We demonstrated that indeed, the kinase domain on the gene fusion were active, and partake in rampant cell signaling. Because drug resistance is common in cancers such as leukemia, the implications from this work may uncover additional methods of therapeutic interventions for patients harboring these types of mutations. Citation Format: Arnel Cardona Ibarra, Vivian Ly, Jason Ear. Understanding the mechanism of Daple-PDGFRB gene fusion in leukemia abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1679.