ReviewLeukemia2003
Resistance of Philadelphia-chromosome positive leukemia towards the kinase inhibitor imatinib (STI571, Glivec): a targeted oncoprotein strikes back.
Review in Leukemia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 112 citations in OpenAlex.
- Significance of Somatic Mutation Profiling in CML Beyond BCR-ABL: A Retrospective Study of the Indian Population.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2025Article
- Discovering and validating cancer genetic dependencies: approaches and pitfalls.Nature reviews. Genetics · 2020Review
- Next-generation sequencing for BCR-ABL1 kinase domain mutations in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position paper.Cancer medicine · 2020Review
- Huai Qi Huang-induced Apoptosis via Down-regulating PRKCH and Inhibiting RAF/MEK/ERK Pathway in PhCurrent medical science · 2020Article
- Adaptive phenotypic modulations lead to therapy resistance in chronic myeloid leukemia cells.PloS one · 2020Article
- Molecular Mechanisms of Resistance to Tyrosine Kinase Inhibitors.Current hematologic malignancy reports · 2019Review
- Structural Variants as a Basis for Targeted Therapies in Hematological Malignancies.Frontiers in oncology · 2019Review
- Anthelmintic niclosamide suppresses transcription of BCR-ABL fusion oncogene via disabling Sp1 and induces apoptosis in imatinib-resistant CML cells harboring T315I mutant.Cell death & disease · 2018Article
- Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Kinase Inhibitors.Hematology/oncology clinics of North America · 2017Review
- Cobll1 is linked to drug resistance and blastic transformation in chronic myeloid leukemia.Leukemia · 2017Article
- Contributions of MET activation to BCR-ABL1 tyrosine kinase inhibitor resistance in chronic myeloid leukemia cells.Oncotarget · 2017Article
- Diagnostic and treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia.International journal of hematologic oncology · 2016Review
- A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia.Science translational medicine · 2014Article
- Identification of drug combinations containing imatinib for treatment of BCR-ABL+ leukemias.PloS one · 2014Article
- Management options for refractory chronic myeloid leukemia: considerations for the elderly.Drugs & aging · 2013Review
- Article
- Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic leukemia and tyrosine kinase inhibitor therapy.World journal of stem cells · 2012Article
- BCR-ABL isoforms associated with intrinsic or acquired resistance to imatinib: more heterogeneous than just ABL kinase domain point mutations?Medical oncology (Northwood, London, England) · 2012Article
- Overcoming CML acquired resistance by specific inhibition of Aurora A kinase in the KCL-22 cell model.Carcinogenesis · 2012Article
- Managing Philadelphia chromosome-positive acute lymphoblastic leukemia: role of tyrosine kinase inhibitors.Clinical lymphoma, myeloma & leukemia · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer research within the last decades elucidated signaling pathways and identified genes and proteins that lead or contribute to malignant transformation of a cell. Discovery of the Bcr-Abl oncoprotein as the molecular abnormality causing chronic myeloid leukemia (CML) paved the way for the development of a targeted anticancer therapy. The substantial activity of imatinib mesylate (STI571, Glivec) in CML and Philadelphia (Ph)-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) changed the therapeutic approach to Ph+ leukemia and rang the bell for a new era of anticancer treatment. However, when the phenomenon of relapse occurred despite continued imatinib treatment, we had to learn the lesson that imatinib can select for a resistant disease clone. If such a clone still depends on Bcr-Abl, it either carries a BCR-ABL point mutation that prevents binding of the drug or expresses the fusion protein at high levels. Alternatively, leukemia cells that harbor secondary genetic alterations resulting in Bcr-Abl-independent proliferation are selected for their growth advantage in the presence of imatinib. Point mutations in the BCR-ABL kinase domain prevent binding of imatinib but still allow binding of ATP, thus retaining Bcr-Abl kinase activity. Mutated BCR-ABL is frequently detected in cases of imatinib-resistant Ph+ leukemia and therefore represents the main challenge for the investigation of alternative strategies to either overcome resistance or to prevent the emergence of a resistant leukemic clone.
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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.