{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T06:59:35Z","timestamp":1761893975897,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T00:00:00Z","timestamp":1090540800000},"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":[[2004,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The objective of the current study was to verify the ability to predict response to imatinib therapy using in vitro assays to evaluate the inhibition of Wilms tumor gene (<jats:italic>WT1<\/jats:italic>) expression and colony growth after samples obtained from patients with chronic myelogenous leukemia (CML) before the start of treatment were subjected to short\u2010term incubation with imatinib.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p><jats:italic>WT1<\/jats:italic> transcript levels and colony growth in bone marrow (BM) samples from 23 patients with CML that was later identified as being responsive to imatinib and from 13 patients with CML that was later identified as not being responsive to imatinib were evaluated after incubation of these samples with imatinib at a concentration of 1 \u03bcM for 18 hours. In addition, real\u2010time quantitative polymerase chain reaction (RQ\u2010PCR) analysis of <jats:italic>WT1<\/jats:italic> expression was performed during follow\u2010up, and the results were analyzed for associations with cytogenetic response and with <jats:italic>BCR\/ABL<\/jats:italic> transcript levels as determined using RQ\u2010PCR analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Before treatment, it was found that <jats:italic>WT1<\/jats:italic> expression was elevated in BM samples obtained from all patients with CML. <jats:italic>WT1<\/jats:italic> expression and colony growth were reduced significantly after an 18\u2010hour incubation with imatinib in samples obtained from patients who were later identified as responders to treatment, but not in samples obtained from patients who did not experience responses to treatment. Inhibition of <jats:italic>WT1<\/jats:italic> expression in vitro was associated with inhibition of imatinib\u2010induced <jats:italic>BCR\u2010ABL<\/jats:italic> tyrosine kinase activity, a finding that also has been made in studies involving certain Philadelphia chromosome (Ph)\u2010positive and Ph\u2010negative cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Inhibition of <jats:italic>WT1<\/jats:italic> transcript levels after a short period of in vitro exposure of pretherapy BM samples to imatinib was correlated with inhibition of colony growth and may represent the basis for an easy test that is capable of predicting the sensitivity of CML to treatment with imatinib for individual patients. Cancer 2004. \u00a9 2004 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.20457","type":"journal-article","created":{"date-parts":[[2004,7,23]],"date-time":"2004-07-23T12:01:07Z","timestamp":1090584067000},"page":"979-988","source":"Crossref","is-referenced-by-count":27,"title":["Sensitivity to imatinib therapy may be predicted by testing Wilms tumor gene expression and colony growth after a short in vitro 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