Zi Wang1, Yong Li1, Xiaokai Lu1, Jia Yuan1, Qiang Qiu2, Cong Pan2,3. 1. Department of Oncology, Guizhou Provincial People's Hospital Guiyang 550002, China. 2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu 610041, China. 3. Chengdu eBond Biomedical Research Center Chengdu 610041, China.
Abstract
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. IJCEP
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. IJCEP
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