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Updated: Nov 27, 2025

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Increased sensitivity of BCR-ABL-induced B-ALL to imatinib by releasing leukemia B cell differentiation blockage
Zi Wang1, Yong Li1, Xiaokai Lu1
1Department of Oncology, Guizhou Provincial People's Hospital Guiyang 550002, China.
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.
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