ArticleLeukemia2004
Imatinib sensitizes CLL lymphocytes to chlorambucil.
Article in Leukemia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I-II Trial of Gleevec (Imatinib Mesylate) in Combination With Chlorambucil in Previously Treated Chronic Lymphocytic Leukemia (CLL) Patients
Open-labeled, Multicenter, Phase I/II Study of Imatinib Combined With ESHAP as Salvage Therapy in Relapsed/Refractory Non-Hodgkin's Lymphoma
Who cites it
17 citing papers in PubMed, 61 citations in OpenAlex.
- Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.British journal of cancer · 2009Trial
- A RUNX-targeted gene switch-off approach modulates the BIRC5/PIF1-p21 pathway and reduces glioblastoma growth in mice.Communications biology · 2022Article
- Brain-invasive meningiomas: molecular mechanisms and potential therapeutic options.Brain tumor pathology · 2021Review
- Case Report: Long-Term Survival of a Dog With Chronic Lymphocytic Leukemia Treated With Chlorambucil, Prednisolone, and Imatinib.Frontiers in veterinary science · 2021Article
- Hybrid inhibitors of DNA and HDACs remarkably enhance cytotoxicity in leukaemia cells.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- DNA Damage/Repair Management in Cancers.Cancers · 2020Review
- Concomitant imatinib and ibrutinib in a patient with chronic myelogenous leukemia and chronic lymphocytic leukemia.Clinical case reports · 2017Article
- Simultaneous inhibition of ATR and PARP sensitizes colon cancer cell lines to irinotecan.Frontiers in pharmacology · 2015Article
- DNA repair dysregulation from cancer driver to therapeutic target.Nature reviews. Cancer · 2012Review
- Article
- Primary del 17 chronic lymphocytic leukaemia lymphocytes are hypersensitive to dasatinib in vitro.British journal of haematology · 2009Article
- Molecular and cellular mechanisms of CLL: novel therapeutic approaches.Nature reviews. Clinical oncology · 2009Review
- Article
- Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma.Neuro-oncology · 2008Article
- Clinical relevance of the homologous recombination machinery in cancer therapy.Cancer science · 2008Review
- The role of DNA repair in chronic lymphocytic leukemia pathogenesis and chemotherapy resistance.Current oncology reports · 2007Review
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The effect of imatinib on chlorambucil (CLB) cytotoxicity in chronic lymphocytic leukemia (CLL) lymphocytes was examined in vitro. Imatinib sensitizes the WSU and I83 human CLL cell lines, 10- and two-fold, respectively, to CLB. Furthermore, in primary cultures of malignant B-lymphocytes obtained from 12 patients with CLL (seven patients were untreated and five treated with CLB), imatinib synergistically sensitized these lymphocytes from two- to 20-fold to CLB. This synergistic effect was observed at concentrations of imatinib (</=10 microM), which are achievable in patients with minimal toxicity. Moreover, the combination of both drugs results in increased apoptosis in CLL cell lines. These results suggest that imatinib should be useful in improving the therapeutic index of CLB in CLL. The mechanism of action appears to involve imatinib inhibition of c-abl kinase activity with an associated decrease in CLB-induced Rad51 phosphorylation and CLB-induced Rad51 nuclear foci, suggesting that imatinib decreases Rad51-related DNA repair of CLB-induced DNA lesions. Altogether, our results suggest that imatinib is a promising adjuvant therapy to CLB treatment of CLL.
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Registered trials
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.