ArticleOncogene2015
CHK1 overexpression in T-cell acute lymphoblastic leukemia is essential for proliferation and survival by preventing excessive replication stress.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- BAYESIAN EMPIRICAL LIKELIHOOD FOR ULTRA-HIGH DIMENSIONAL VARIABLE SELECTION WITH APPLICATION TO DRUG SENSITIVITY.The annals of applied statistics · 2026Article
- BANF1 at the crossroads of genome stability and innate immunity: emerging implications for hematologic malignancies.Frontiers in immunology · 2026Review
- DNA repair and the contribution to chemotherapy resistance.Genome medicine · 2025Review
- Discovery of key molecular signatures for diagnosis and therapies of glioblastoma by combining supervised and unsupervised learning approaches.Scientific reports · 2024Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Clinical evidence for a role of E2F1-induced replication stress in modulating tumor mutational burden and immune microenvironment.DNA repair · 2023Article
- Studying the DNA damage response pathway in hematopoietic canine cancer cell lines, a necessary step for finding targets to generate new therapies to treat cancer in dogs.Frontiers in veterinary science · 2023Article
- Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.Nature cancer · 2022Article
- Preclinical efficacy of prexasertib in acute lymphoblastic leukemia.British journal of haematology · 2021Article
- Fms-like tyrosine kinase 3-internal tandem duplications epigenetically activates checkpoint kinase 1 in acute myeloid leukemia cells.Scientific reports · 2021Article
- Targeting Non-Oncogene Addiction for Cancer Therapy.Biomolecules · 2021Review
- Checkpoint kinase‑1 inhibition and etoposide exhibit a strong synergistic anticancer effect on chronic myeloid leukemia cell line K562 by impairing homologous recombination DNA damage repair.Oncology reports · 2020Article
- Targeting DNA Repair Pathways in Hematological Malignancies.International journal of molecular sciences · 2020Review
- Article
- Direct regulation of Chk1 protein stability by E3 ubiquitin ligase HUWE1.The FEBS journal · 2020Article
- Investigating the inhibitory effect of miR-34a, miR-449a, miR-1827, and miR-106b on target genes including NOTCH1, c-Myc, and CCND1 in human T cell acute lymphoblastic leukemia clinical samples and cell line.Iranian journal of basic medical sciences · 2020Article
- Cell Cycle Genes Are Potential Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma.BioMed research international · 2020Article
- Clinical and functional significance of CHK1-S, an alternatively spliced isoform of the CHK1 gene, in hepatocellular carcinoma.Journal of Cancer · 2020Article
- Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Nbn-Mre11 interaction is required for tumor suppression and genomic integrity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Checkpoint kinase 1 (CHK1) is a key component of the ATR (ataxia telangiectasia-mutated and Rad3-related)-dependent DNA damage response pathway that protect cells from replication stress, a cell intrinsic phenomenon enhanced by oncogenic transformation. Here, we show that CHK1 is overexpressed and hyperactivated in T-cell acute lymphoblastic leukemia (T-ALL). CHEK1 mRNA is highly abundant in patients of the proliferative T-ALL subgroup and leukemia cells exhibit constitutively elevated levels of the replication stress marker phospho-RPA32 and the DNA damage marker γH2AX. Importantly, pharmacologic inhibition of CHK1 using PF-004777736 or CHK1 short hairpin RNA-mediated silencing impairs T-ALL cell proliferation and viability. CHK1 inactivation results in the accumulation of cells with incompletely replicated DNA, ensuing DNA damage, ATM/CHK2 activation and subsequent ATM- and caspase-3-dependent apoptosis. In contrast to normal thymocytes, primary T-ALL cells are sensitive to therapeutic doses of PF-004777736, even in the presence of stromal or interleukin-7 survival signals. Moreover, CHK1 inhibition significantly delays in vivo growth of xenotransplanted T-ALL tumors. We conclude that CHK1 is critical for T-ALL proliferation and viability by downmodulating replication stress and preventing ATM/caspase-3-dependent cell death. Pharmacologic inhibition of CHK1 may be a promising therapeutic alternative for T-ALL treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.