{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:27:33Z","timestamp":1781108853599,"version":"3.54.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"50","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,12,14]]},"abstract":"<jats:p>\n                    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 \u03b1 and \u03b2, 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-\n                    <jats:italic>tert<\/jats:italic>\n                    -butyl-3-(1-naphthyl)pyrazolo[3,4-\n                    <jats:sc>d<\/jats:sc>\n                    ]pyrimidine and used it to demonstrate that sole suppression of BCR-ABL activity was insufficient to eliminate BCR-ABL\n                    <jats:sup>+<\/jats:sup>\n                    KIT\n                    <jats:sup>+<\/jats:sup>\n                    -expressing immature murine myeloid leukemic cells. In contrast, imatinib mesylate effectively eliminated BCR-ABL\n                    <jats:sup>+<\/jats:sup>\n                    KIT\n                    <jats:sup>+<\/jats:sup>\n                    -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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0407061101","type":"journal-article","created":{"date-parts":[[2004,10,25]],"date-time":"2004-10-25T20:16:44Z","timestamp":1098735404000},"page":"17456-17461","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations"],"prefix":"10.1073","volume":"101","author":[{"given":"S.","family":"Wong","sequence":"first","affiliation":[{"name":"Molecular Biology Interdepartmental Ph.D. Program, Department of Microbiology, Immunology and Molecular Genetics, and Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Molecular Biology Interdepartmental Ph.D. Program, Department of Microbiology, Immunology and Molecular Genetics, and Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Cheng","sequence":"additional","affiliation":[{"name":"Molecular Biology Interdepartmental Ph.D. Program, Department of Microbiology, Immunology and Molecular Genetics, and Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Molecular Biology Interdepartmental Ph.D. Program, Department of Microbiology, Immunology and Molecular Genetics, and Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095; and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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