Prediction of sensitivity to STI571 among chronic myeloid leukemia patients by genome-wide cDNA microarray analysis.
One of the most critical issues to be solved in regard to cancer chemotherapy is the establishment of ways to predict the efficacy of anti-cancer drugs for individual patients. To develop a prediction system based on expression of specific genes, we analyzed expression profiles of mononuclear cells from 18 chronic myeloid leukemia (CML) patients who were treated with the tyrosine kinase inhibitor STI571. cDNA microarrays representing 23 040 genes identified 79 genes that were expressed differentially between responders and non-responders to STI571. On the basis of the expression patterns of 15 or 30 of these genes among the patients, we developed a "Prediction Score" system that could clearly separate the responder group from the non-responder group. Verification of this system using four additional ("test") cases succeeded in predicting the response of each of those four patients to the drug. These results provide the first evidence that gene-expression profiles can predict sensitivity of CML cells to STI571, and may eventually lead to the achievement of "personalized therapy" for this disease.
Kaneta
Yasuyuki
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Kagami
Yoshitoyo
Y
Katagiri
Toyomasa
T
Tsunoda
Tatsuhiko
T
Jin-nai
Itsuro
I
Taguchi
Hirokuni
H
Hirai
Hisamaru
H
Ohnishi
Kazunori
K
Ueda
Takanori
T
Emi
Nobuhiko
N
Tomida
Akihiro
A
Tsuruo
Takashi
T
Nakamura
Yusuke
Y
Ohno
Ryuzo
R
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate