In vitro drug resistance to imatinib and mutation of ABL gene in childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia.
Imatinib, the ABL kinase inhibitor, is used not only for Philadelphia chromosome-positive (Ph + ) chronic myelogenous leukemia, but also for Ph + acute lymphoblastic leukemia (ALL), although resistance to the drug tends to develop in an early stage of the clinical course. We describe a childhood refractory Ph + ALL patient in whom progressive resistance to imatinib was correlated with the appearance of a mutation in the BCR-ABL kinase domain and in vitro drug resistance to imatinib as determined by the methyl-thiazol-tetrazolium (MTT) assay. A missense mutation of T to C (Y253H) of the ABL gene was identified in the resistant clone, suggesting that this mutation may play an etiological role in the rapid loss of drug sensitivity.
Kawaguchi
Hiroyuki
H
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Japan.
Taketani
Takeshi
T
Hongo
Teruaki
T
Park
Myoung-Ja
MJ
Koh
Katsuyoshi
K
Ida
Kohmei
K
Kobayashi
Miyuki
M
Takita
Junko
J
Taki
Tomohiko
T
Yoshino
Hiroshi
H
Bessho
Fumio
F
Hayashi
Yasuhide
Y
D001549:Benzamides; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016313:Genes, abl / Q000235:genetics* / Q000502:physiology; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D020125:Mutation, Missense; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate