The ba/f3 transformation assay: characterization of a novel csf2rb-activating variant, and the discovery of acquired mutations in ba/f3 cells

In this dissertation, the discovery of the first CSF2RB-activating human variant found in the germline of a pediatric T-cell acute lymphoblastic leukemia patient is presented. In vitro, CSF2RB R461C transforms Ba/F3 cells to factor-independent growth through ligand- independent activation and stabilization of CSF2RB. CSF2RB R461C increases downstream 2 activation of JAK2/STAT-5, and inhibition of JAK2 results in apoptosis, making this a potentially actionable clinical variant.