Trial reportLeukemia2002
Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy.
Trial report in Leukemia, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 274 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
274 citing papers in PubMed, 2 syntheses or guidelines pooled it, 901 citations in OpenAlex.
- Emergence of BCR-ABL kinase domain mutations associated with newly diagnosed chronic myeloid leukemia: a meta-analysis of clinical trials of tyrosine kinase inhibitors.Journal of managed care & specialty pharmacy · 2015Pooled it
- Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Guideline
- An enhanced genetic model of relapsed IGH-translocated multiple myeloma evolutionary dynamics.Blood cancer journal · 2020Trial
- Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors.Haematologica · 2014Trial
- Trial
- Long-term pattern of pleural effusion from chronic myeloid leukemia patients in second-line dasatinib therapy.International journal of hematology · 2011Trial
- Trial
- Trial
- Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2009Trial
- Phase 1/2 clinical study of dasatinib in Japanese patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.International journal of hematology · 2009Trial
- Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia.Leukemia · 2007Trial
- Targeting the eIF4F translation initiation complex disrupts BCR::ABL1 translation and overcomes drug resistance in CML.Leukemia · 2026Article
- Review
- From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia.Leukemia · 2026Review
- Article
- Proximity-Induced Rewiring of Oncogenic Kinase Triggers Apoptosis.ACS central science · 2026Article
- Roles of extracellular vesicles in the pathogenesis of chronic myeloid leukemia.Journal of physiology and biochemistry · 2026Review
- Review
- Chronic Myeloid Leukemia and the T315IInternational journal of molecular sciences · 2025Review
214 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective inhibition of the BCR-ABL tyrosine kinase by imatinib (STI571, Glivec/Gleevec) is a promising new therapeutic strategy in patients with chronic myelogenous leukemia (CML). Despite significant hematologic and cytogenetic responses, resistance occurs, particularly in patients with advanced disease. We sought to determine the underlying mechanisms. Sixty-six patients with CML in myeloid blast crisis (n = 33), lymphoid blast crisis (n = 2), accelerated phase (n = 16), chronic phase (n = 13), and BCR-ABL-positive acute lymphoblastic leukemia (n = 2) resistant to imatinib were investigated. Median duration of imatinib therapy was 148 days (range 6-882). Patients were evaluated for genomic amplification of BCR-ABL, overexpression of BCR-ABL transcripts, clonal karyotypic evolution, and mutations of the imatinib binding site in the BCR-ABL tyrosine kinase domain. Results were as follows: (1) Median levels of BCR-ABL transcripts, were not significantly changed at the time of resistance but 7/55 patients showed a >10-fold increase in BCR-ABL levels; (2) genomic amplification of BCR-ABL was found in 2/32 patients evaluated by fluorescence in situ hybridization; (3) additional chromosomal aberrations were observed in 19/36 patients; (4) point mutations of the ABL tyrosine kinase domain resulting in reactivation of the BCR-ABL tyrosine kinase were detected in 23/66 patients. In conclusion, although the heterogeneous development of imatinib resistance is challenging, the fact that BCR-ABL is active in many resistant patients suggests that the chimeric oncoprotein remains a good therapeutic target. However, patients with clonal evolution are more likely to have BCR-ABL-independent mechanisms of resistance. The observations warrant trials combining imatinib with other agents.
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What OpenQuestion holds
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.