ArticlePLoS genetics2014
ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Understanding the Role of All-Trans Retinoic Acid in Acute Myeloid Leukemia Cells.World journal of oncology · 2025Article
- All-trans Retinoic Acid Sensitizes Epithelial Ovarian Cancer to PARP Inhibition after Exposure to Cisplatin.Molecular cancer therapeutics · 2025Article
- The mGenes & diseases · 2024Article
- Molecular Determinants Underlying the Anti-Cancer Efficacy of CD38 Monoclonal Antibodies in Hematological Malignancies.Biomolecules · 2022Review
- Somatic Mutations in Oncogenes Are in Chronic Myeloid Leukemia AcquiredFrontiers in oncology · 2021Article
- PVR and ICAM-1 on Blast Crisis CML Stem and Progenitor Cells with TKI Resistance Confer Susceptibility to NK Cells.Cancers · 2020Article
- Nicotinic-nAChR signaling mediates drug resistance in lung cancer.Journal of Cancer · 2020Review
- Article
- BCR-ABL enhances the prolyl isomerase activity of Pin 1 by interacting with DAPK1 in phCancer medicine · 2018Article
- c-MYC and reactive oxygen species play roles in tetrandrine-induced leukemia differentiation.Cell death & disease · 2018Article
- Molecular screening and the clinical impacts of BCR-ABL KD mutations in patients with imatinib-resistant chronic myeloid leukemia.Oncology letters · 2018Article
- Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition.Scientific reports · 2017Article
- Smad inhibitor induces CSC differentiation for effective chemosensitization in cyclin D1- and TGF-β/Smad-regulated liver cancer stem cell-like cells.Oncotarget · 2017Article
- Detection approaches for multidrug resistance genes of leukemia.Drug design, development and therapy · 2017Review
- SIRT1 and LSD1 competitively regulate KU70 functions in DNA repair and mutation acquisition in cancer cells.Oncotarget · 2016Article
- Effect of CD38 on the multidrug resistance of human chronic myelogenous leukemia K562 cells to doxorubicin.Oncology letters · 2016Article
- CD150(-) Side Population Defines Leukemia Stem Cells in a BALB/c Mouse Model of CML and Is Depleted by Genetic Loss of SIRT1.Stem cells (Dayton, Ohio) · 2015Article
- UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib.International journal of molecular sciences · 2015Article
- Role of SIRT1 in the growth and regulation of normal hematopoietic and leukemia stem cells.Current opinion in hematology · 2015Review
- Correction: ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance.PLoS genetics · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Acquired resistance through genetic mutations is a major obstacle in targeted cancer therapy, but the underlying mechanisms are poorly understood. Here we studied mechanisms of acquired resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) by examining genome-wide gene expression changes in KCL-22 CML cells versus their resistant KCL-22M cells that acquire T315I BCR-ABL mutation following TKI exposure. Although T315I BCR-ABL is sufficient to confer resistance to TKIs in CML cells, surprisingly we found that multiple drug resistance pathways were activated in KCL-22M cells along with reduced expression of a set of myeloid differentiation genes. Forced myeloid differentiation by all-trans-retinoic acid (ATRA) effectively blocked acquisition of BCR-ABL mutations and resistance to the TKIs imatinib, nilotinib or dasatinib in our previously described in vitro models of acquired TKI resistance. ATRA induced robust expression of CD38, a cell surface marker and cellular NADase. High levels of CD38 reduced intracellular nicotinamide adenine dinucleotide (NAD+) levels and blocked acquired resistance by inhibiting the activity of the NAD+-dependent SIRT1 deacetylase that we have previously shown to promote resistance in CML cells by facilitating error-prone DNA damage repair. Consequently, ATRA treatment decreased DNA damage repair and suppressed acquisition of BCR-ABL mutations. This study sheds novel insight into mechanisms underlying acquired resistance in CML, and suggests potential benefit of combining ATRA with TKIs in treating CML, particularly in advanced phases.
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