Prediction of response to imatinib by cDNA microarray analysis.
Clinical introduction of imatinib mesylate (Gleevec) (formerly STI571) has marked a major advance in the treatment of chronic myeloid leukemia (CML), inducing major cytogenetic response in 60% to 80% of patients with chronic-phase disease. Since its remarkable effect has made it difficult to decide the timing for potentially curative but life-threatening stem cell transplantation (SCT), it would be very useful to predict imatinib's effectiveness in individual patients beforehand. We analyzed gene expression profiles of peripheral leukemia cells from 18 CML patients (16 chronic phase, two blast crisis) who were treated with imatinib alone. cDNA microarrays representing 23,040 genes identified 79 genes that were expressed differentially between cytogenetically defined responders and nonresponders to imatinib. We then established a "prediction score" system using 15 or 30 of these genes that could clearly separate the responder group from the nonresponder group. Four additional patients' responses to imatinib were successfully predicted, validating the process. Thus, gene-expression profiles can predict clinical effectiveness of CML to imatinib, and may eventually lead to the achievement of "personalized therapy" for this disease.
Ohno
Ryuzo
R
Aichi Cancer Center Hospital, Nagoya, Japan; and the Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nakamura
Yusuke
Y
D000328:Adult; D000368:Aged; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate