Role of the Adapter Protein 3BP2 in BCR-ABL-mediated Signal Transduction and Leukemogenesis

• Main Author: Jarvis, Jordan
• Other Authors: Barber, Dwayne
• Language: en_ca
• Published: 2012
• Subjects: leukemia; signal transduction; BCR-ABL; 3BP2; 0307
• Online Access: http://hdl.handle.net/1807/33254

3BP2 was originally identified through its interaction with the ABL kinase. Fusion of ABL with the BCR gene forms the BCR-ABL onco-protein, which is causative in Chronic Myeloid Leukemia (CML) and acute lymphoid leukemia (ALL). Due to the ability of 3BP2 to regulate ABL activity in osteoblasts, we hypothesize that 3BP2 modulates BCR-ABL signalling. Overexpression of 3BP2 in the CML-T1 cell line produced a marked decrease in global tyrosine phosphorylation. 3BP2 overexpression also resulted in a significant increase in CML-T1 cell growth, accompanied by altered ERK1/2, AKT, SYK, LYN, HCK, and CBL phosphorylation and expression. A phospho-SRC family protein and a 116 kDa phospho-protein were identified as 3BP2 interaction partners in response to BCR-ABL activation. BCR-ABL bone marrow transplantation (BMT) models in 3bp2-/- mice exhibit accelerated disease compared to wild-type mice, with altered leukemic phenotype. In conclusion, 3BP2 is able to modulate signalling through BCR-ABL and affect BCR-ABL-induced disease outcome.