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Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639 [J-i. O., Y. Ka., T. K., O. K., H. Z., R. Y., Y. N.]; Laboratory of Medical Informatics, SNP Research Center, RIKEN (Institute of Physical and Chemical Research), Tokyo 108-8639 [T. Ts.]; Department of Medicine, Saiseikai Maebashi Hospital, Maebashi 371-0821 [S. M.]; Department of Hematology and Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Nagasaki 852-8102 [K. Kur.]; Tokai University School of Medicine, Isehara 259-1100 [N. K.]; First Department of Internal Medicine, Tokyo Medical University, Tokyo 160-0023 [Y. Ki.]; Aomori Prefectural Central Hospital, Aomori 030-0913 [K. Kub.]; First Department of Internal Medicine, Saitama-Medical School, Saitama 350-0495 [F. Y.]; Department of Internal Medicine, Sapporo Hokuyu Hospital, Shiroishi-ku, Sapporo 003-0006 [T. H.]; Third Department of Internal Medicine, Kochi Medical School, Kochi 783-0043 [H. T.]; Department of Hematology, Yaizu City Hospital, Yaizu [T. To.]; Tokyo Metropolitan Komagome Hospital, Tokyo 113-0024 [H. K.]; Department of Internal Medicine III, Hamamatsu University, School of Medicine, Hamamatsu 431-3192 [A. T.]; Department of Hematology, Tokyo Women’s Medical University, Tokyo 162-0054 [Y-H. W., T. M.]; Aichi Cancer Center, Nagoya 464-0021 [R. O.], Japan

To identify genes involved in the sensitivity of acute myeloid leukemia (AML) cells to chemotherapy, we monitored gene-expression profiles of cancer cells from 76 AML patients using a cDNA microarray consisting of 23,040 genes. We identified 63 genes that were commonly overexpressed and 372 genes suppressed in AML. Because these genes represent key molecules for disclosing the molecular mechanisms of AML, they may be potential targets for drug development. We also found 28 that revealed different expression levels between good and poor responders to chemotherapy and appeared to be associated with chemosensitivity. On that basis, we developed a "Drug Response Scoring" system that was correlated well with individual sensitivity to an anticancer drug regimen. Among the 44 cases with positive drug-response scores by our definition, 40 achieved complete remission after treatment, whereas the only 3 of the 20 cases with negative scores responded well to the treatment. An ability to predict chemosensitivity should eventually lead to achievement of our goal of "personalized therapy."

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