{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:06:14Z","timestamp":1760706374507,"version":"build-2065373602"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2002,5,14]],"date-time":"2002-05-14T00:00:00Z","timestamp":1021334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Chronic myelogenous leukemia (CML) is characterized by a molecular aberration, a fusion <jats:italic>BCR\u2010ABL<\/jats:italic> gene encoding for aberrant tyrosine kinase activity, which is crucial in the pathogenesis of CML. In vitro, inhibition of BCR\u2010ABL protein tyrosine kinase activity by a tyrosine kinase inhibitor, Imatinib mesylate (STI571; formerly CGP57148B), successfully suppressed proliferation\/survival of the BCR\u2010ABL positive clones. In clinical studies, hematologic and cytogenetic remissions have been achieved in most patients with chronic phase CML; in accelerated and blastic phases of CML, STI571 appeared less effective. In the current study, the authors tested combinations of STI571 and cytarabine and homoharringtonine (HHT), drugs with documented activity in CML.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The single agents and their combinations were studied for in vitro effect on proliferation of BCR\u2010ABL positive cell lines KBM5 and KBM7 by 3(4,5\u2010dimethylthiazol\u20102yl)\u20102,5 diphenyl\u2010tetrazolium bromide assay and on primary patient\u2010derived BCR\u2010ABL cells by clonogenic assays. The in vitro additive, synergistic, or antagonistic effects of cytarabine and HHT with STI571 were then investigated by computer\u2010assisted analysis using the CalcuSyn software.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>STI571 consistently suppressed BCR\u2010ABL positive cell proliferation with a dose\u2010effect correlation. In the model system used, STI571\/cytarabine and STI571\/HHT combinations were more effective in inhibiting KBM5 and KBM7 cell growth than each drug as single agent. These results were also verified in primary CML\u2010derived clonogenic cells in semisolid cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>In this experimental system, our studies documented additive or synergistic effects with STI571 plus cytarabine or HHT, supporting the future use of STI571 combinations in clinical trials in patients with Philadelphia chromosome\u2010positive leukemias. Cancer 2002;94:2653\u201362. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.10543<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.10543","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T19:28:18Z","timestamp":1030303698000},"page":"2653-2662","source":"Crossref","is-referenced-by-count":48,"title":["In vitro effects of STI 571\u2010containing drug combinations on the growth of Philadelphia\u2010positive chronic myelogenous leukemia cells"],"prefix":"10.1002","volume":"94","author":[{"given":"Barbara","family":"Scappini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Onida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagop 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