Deletion of the ABL SH3 domain reactivates de-oligomerized BCR-ABL for growth factor independence.

Biological activities of BCR-ABL, an activated tyrosine kinase oncogene responsible for pathogenesis of human leukemias, can be completely inactivated by a deletion of the BCR aminoterminal sequence with tetramerizing property (BCR-ABL delta 1-40). We attempted several ways to restore the ability to induce growth factor independence to the de-oligomerized BCR-ABL delta 1-40 and found that an additional deletion of the ABL SH3 domain could. In BCR-ABL delta 1-40 reactivated by the SH3 deletion, transphosphoryation of other cellular proteins like p62 or SHC in vivo and autophosphorylation with recruitment of GRB-2 were also recovered.