ArticleThe Journal of biological chemistry2010
BCR-ABL gene expression is required for its mutations in a novel KCL-22 cell culture model for acquired resistance of chronic myelogenous leukemia.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- Targeting cytokine-induced leukemic stem cell persistence in chronic myeloid leukemia by IKK2-inhibition.Haematologica · 2023Article
- BH3 mimetics in combination with nilotinib or ponatinib represent a promising therapeutic strategy in blast phase chronic myeloid leukemia.Cell death discovery · 2022Article
- Introduction of the T315I gatekeeper mutation of BCR/ABL1 into a Philadelphia chromosome-positive lymphoid leukemia cell line using the CRISPR/Cas9 system.International journal of hematology · 2022Article
- Rotating between ponatinib and imatinib temporarily increases the efficacy of imatinib as shown in a chronic myeloid leukaemia model.Scientific reports · 2022Article
- Article
- Recent advances of SIRT1 and implications in chemotherapeutics resistance in cancer.American journal of cancer research · 2021Review
- Somatic Mutations in Oncogenes Are in Chronic Myeloid Leukemia AcquiredFrontiers in oncology · 2021Article
- Asciminib and ponatinib exert synergistic anti-neoplastic effects on CML cells expressingAmerican journal of cancer research · 2021Article
- Inferring time-dependent population growth rates in cell cultures undergoing adaptation.BMC bioinformatics · 2020Article
- PVR and ICAM-1 on Blast Crisis CML Stem and Progenitor Cells with TKI Resistance Confer Susceptibility to NK Cells.Cancers · 2020Article
- CDK4/CDK6 inhibition as a novel strategy to suppress the growth and survival of BCR-ABL1EBioMedicine · 2019Article
- A kinase profile-adapted drug combination elicits synergistic cooperative effects on leukemic cells carrying BCR-ABL1Leukemia research · 2019Article
- Novel mutations in the kinase domain of BCR-ABL gene causing imatinib resistance in chronic myeloid leukemia patients.Scientific reports · 2019Article
- BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia.Haematologica · 2018Article
- T315I mutation of BCR-ABL1 into human Philadelphia chromosome-positive leukemia cell lines by homologous recombination using the CRISPR/Cas9 system.Scientific reports · 2018Article
- Alkynylnicotinamide-Based Compounds as ABL1 Inhibitors with Potent Activities against Drug-Resistant CML Harboring ABL1(T315I) Mutant Kinase.ChemMedChem · 2018Article
- Connexin 32 and connexin 43 are involved in lineage restriction of hepatic progenitor cells to hepatocytes.Stem cell research & therapy · 2017Article
- Natural-Based Indirubins Display Potent Cytotoxicity toward Wild-Type and T315I-Resistant Leukemia Cell Lines.Journal of natural products · 2016Article
- Cooperation of imipramine blue and tyrosine kinase blockade demonstrates activity against chronic myeloid leukemia.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired resistance through genetic mutations is a common phenomenon in several cancer therapies using molecularly targeted drugs, best exemplified by the BCR-ABL inhibitor imatinib in treating chronic myelogenous leukemia (CML). Overcoming acquired resistance is a daunting therapeutic challenge, and little is known about how these mutations evolve. To facilitate understanding the resistance mechanisms, we developed a novel culture model for CML acquired resistance in which the CML cell line KCL-22, following initial response to imatinib, develops resistant T315I BCR-ABL mutation. We demonstrate that the emergence of BCR-ABL mutations do not require pre-existing BCR-ABL mutations derived from the original patient as the subclones of KCL-22 cells can form various BCR-ABL mutations upon imatinib treatment. BCR-ABL mutation rates vary from cell clone to clone and passages, in contrast to the relatively stable mutation rate of the hypoxanthine-guanine phosphoribosyltransferase gene. Strikingly, development of BCR-ABL mutations depends on its gene expression because BCR-ABL knockdown completely blocks KCL-22 cell relapse on imatinib and acquisition of mutations. We further show that the endogenous BCR-ABL locus has significantly higher mutagenesis potential than the transduced randomly integrated BCR-ABL cDNA. Our study suggests important roles of BCR-ABL gene expression and its native chromosomal locus for acquisition of BCR-ABL mutations and provides a new tool for further studying resistance mechanisms.
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