Increased sensitivity of BCR-ABL-induced B-ALL to imatinib by releasing leukemia B cell differentiation blockage.

AIMS In B cell acute lymphocytic leukemia (B-ALL), B cells are blocked mainly at the pro/pre-B phase, making them poorly responsive to imatinib. We aimed to investigate whether it was possible to promote pro/pre-B cell maturation beyond this phase and make them sensitive to imatinib treatment by overexpressing immunoregulatory tyrosine activation motif (ITAM) with BCR-ABL in a Ph+ B-ALL mouse model. MATERIALS & METHODS Ph+ B-ALL mouse models were induced by BCR-ABL using retroviral transduction/transplantation. RESULTS Overexpression of ITAM promoted the differentiation of blocked pro/pre-B cells to B220+IgM+ and increased disease sensitivity to imatinib in mice. Btk deficiency accelerated the progression of BCR-ABL-induced B-ALL. CONCLUSION B-cell development blockage released by ITAM renders leukemia cells sensitive to imatinib treatment in BCR-ABL-induced B-ALL.