ArticleOncogene2013
MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1.).
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 50 citations in OpenAlex.
- CTCF Regulates Erythroid Differentiation Through Control of Core Erythroid Transcription Factors.Biomolecules · 2026Article
- CDK8/19 inhibition attenuates G1 arrest induced by BCR-ABL antagonists and accelerates death of chronic myelogenous leukemia cells.Cell death discovery · 2025Article
- Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Genes & diseases · 2024Review
- Titanium dioxide nanostructure-loaded Adriamycin surmounts resistance in breast cancer therapy: ABCA/P53/C-myc crosstalk.Future science OA · 2024Article
- AXL upregulates c‑Myc expression through AKT and ERK signaling pathways in breast cancers.Molecular and clinical oncology · 2023Article
- Cabozantinib promotes erythroid differentiation in K562 erythroleukemia cells through global changes in gene expression and JNK activation.Cancer gene therapy · 2022Article
- The Downregulation of Both Giant HERCs,Journal of clinical medicine · 2022Article
- Statins Enhance the Molecular Response in Chronic Myeloid Leukemia when Combined with Tyrosine Kinase Inhibitors.Cancers · 2021Article
- Review
- Understanding and Monitoring Chronic Myeloid Leukemia Blast Crisis: How to Better Manage Patients.Cancer management and research · 2021Review
- Let-7b downgrades CCND1 to repress osteogenic proliferation and differentiation of MC3T3-E1 cells: An implication in osteoporosis.The Kaohsiung journal of medical sciences · 2020Article
- Cross-talk between Bcr-abl and the Thioredoxin System in Chronic Myeloid Leukaemia: Implications for CML Treatment.Antioxidants (Basel, Switzerland) · 2020Article
- Review
- FHIT and C-MYC expression in cervical histology and cytology as biomarkers for detecting high-grade intraepithelial neoplasia in human papillomavirus-positive women.Cancer biomarkers : section A of Disease markers · 2020Article
- Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index MethodBalkan medical journal · 2019Article
- Transcriptional upregulation of c-MYC by AXL confers epirubicin resistance in esophageal adenocarcinoma.Molecular oncology · 2018Article
- Role of ZNF224 in c-Myc repression and imatinib responsiveness in chronic myeloid leukemia.Oncotarget · 2018Article
- Prognostic significance of MYCN gene amplification and protein expression in primary brain tumors: Astrocytoma and meningioma.Cancer biomarkers : section A of Disease markers · 2017Article
- IRES inhibition induces terminal differentiation and synchronized death in triple-negative breast cancer and glioblastoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients.International journal of oncology · 2016Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic myeloid leukemia (CML) progresses from a chronic to a blastic phase where the leukemic cells are proliferative and undifferentiated. The CML is nowadays successfully treated with BCR-ABL kinase inhibitors as imatinib and dasatinib. In the CML-derived K562 cell line, low concentrations of imatinib induce proliferative arrest and erythroid differentiation. We found that imatinib upregulated the cell cycle inhibitor p27(KIP1) (p27) in a time- and -concentration dependent manner, and that the extent of imatinib-mediated differentiation was severely decreased in cells with depleted p27. MYC (c-Myc) is a transcription factor frequently deregulated in human cancer. MYC is overexpressed in untreated CML and is associated to poor response to imatinib. Using K562 sublines with conditional MYC expression (induced by Zn(2+) or activated by 4-hydroxy-tamoxifen) we show that MYC prevented the erythroid differentiation induced by imatinib and dasatinib. The differentiation inhibition is not due to increased proliferation of MYC-expressing clones or enhanced apoptosis of differentiated cells. As p27 overexpression is reported to induce erythroid differentiation in K562, we explored the effect of MYC on imatinib-dependent induction of p27. We show that MYC abrogated the imatinib-induced upregulation of p27 concomitantly with the differentiation inhibition, suggesting that MYC inhibits differentiation by antagonizing the imatinib-mediated upregulation of p27. This effect occurs mainly by p27 protein destabilization. This was in part due to MYC-dependent induction of SKP2, a component of the ubiquitin ligase complex that targets p27 for degradation. The results suggest that, although MYC deregulation does not directly confer resistance to imatinib, it might be a factor that contributes to progression of CML through the inhibition of differentiation.
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