ArticleProceedings of the National Academy of Sciences of the United States of America2004
Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
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Who cites it
36 citing papers in PubMed, 71 citations in OpenAlex.
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- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Advancements in chemical biology targeting the kinases and phosphatases of RNA polymerase II-mediated transcription.Current opinion in chemical biology · 2021Review
- A chemical-genetics approach to study the role of atypical Protein Kinase C inDevelopment (Cambridge, England) · 2019Article
- Engineering and Functional Analysis of Mitotic Kinases Through Chemical Genetics.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Sirtuin inhibitors as anticancer agents.Future medicinal chemistry · 2014Review
- Clinical targeting of mutated and wild-type protein tyrosine kinases in cancer.Molecular and cellular biology · 2014Review
- Kinase-independent mechanisms of resistance of leukemia stem cells to tyrosine kinase inhibitors.Stem cells translational medicine · 2014Review
- Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth.PLoS pathogens · 2014Article
- A conserved water-mediated hydrogen bond network defines bosutinib's kinase selectivity.Nature chemical biology · 2014Article
- Deoxycytidine kinase augments ATM-Mediated DNA repair and contributes to radiation resistance.PloS one · 2014Article
- Subfamily-specific adaptations in the structures of two penicillin-binding proteins from Mycobacterium tuberculosis.PloS one · 2014Article
- Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.Nature immunology · 2013Article
- KIT signaling governs differential sensitivity of mature and primitive CML progenitors to tyrosine kinase inhibitors.Cancer research · 2013Article
- Pushing the limits of targeted therapy in chronic myeloid leukaemia.Nature reviews. Cancer · 2012Review
- HIV-1 Nef interaction influences the ATP-binding site of the Src-family kinase, Hck.BMC chemical biology · 2012Article
- The PI-3 kinase-Akt-MDM2-survivin signaling axis in high-risk neuroblastoma: a target for PI-3 kinase inhibitor intervention.Cancer chemotherapy and pharmacology · 2011Article
- Validating cancer drug targets through chemical genetics.Biochimica et biophysica acta · 2010Review
- Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner.The Journal of biological chemistry · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Protein kinase inhibitors can be effective in treating selected cancers, but most suppress several kinases. Imatinib mesylate has been useful in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia and B cell acute lymphoblastic leukemia through the inhibition of BCR-ABL tyrosine kinase activity. Imatinib mesylate has also been shown to inhibit KIT, ARG, and platelet-derived growth factor receptors alpha and beta, and potentially other tyrosine kinases. We have produced a mutant allele of BCR-ABL (T315A) that is uniquely inhibitable by the small molecule 4-amino-1-tert-butyl-3-(1-naphthyl)pyrazolo[3,4-d]pyrimidine and used it to demonstrate that sole suppression of BCR-ABL activity was insufficient to eliminate BCR-ABL(+) KIT(+)-expressing immature murine myeloid leukemic cells. In contrast, imatinib mesylate effectively eliminated BCR-ABL(+) KIT(+)-expressing leukemic cells. In the cellular context of mature myeloid cells and Pro/Pre B cells that do not express KIT, monospecific BCR-ABL inhibition was quantitatively as effective as imatinib mesylate in suppressing cell growth and inducing apoptosis. These results suggest that the therapeutic effectiveness of small molecule drugs such as imatinib mesylate could be due to the inhibitor's ability to suppress protein kinases in addition to the dominant target.
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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.