title: A Convenient Cell Culture Model for CML Acquired Resistance Through BCR-ABL Mutations.
abstract: Tyrosine kinase inhibitors (TKIs) are the effective treatments for chronic myeloid leukemia (CML). However, clinical resistance to TKIs that leads to patient relapse remains a challenge. Acquisition of BCR-ABL mutations is crucial in the resistance but the underlying molecular mechanisms are poorly understood. Here we describe a cell culture model for CML acquired resistance in which blast crisis CML cells undergo initial apoptosis upon treatment with therapeutically effective doses of TKIs, but the cells regrow quickly with development of resistance through BCR-ABL mutations. This model mimics the clinical process of acquisition of BCR-ABL mutations and will be an important tool to dissect molecular mechanisms of CML drug resistance and to explore strategies to overcome resistance.
authors: Department of Cancer Biology, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA.
authors: Zhiqiang
authors: Z
authors: Wang
authors: Department of Cancer Biology, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. wechen@coh.org.
authors: WenYong
authors: W
authors: Chen
mesh_terms: D017209:Apoptosis; D001752:Blast Crisis / Q000473:pathology; D045744:Cell Line, Tumor; D000069439:Dasatinib / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D008954:Models, Biological; D009154:Mutation; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib
keywords: Acquired resistance; BCR-ABL; Chronic myeloid leukemia; Colony formation assay; Mutation