In vitro drug resistance to imatinib and mutation of ABL gene in childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia

Hiroyuki Kawaguchi Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Takeshi Taketani Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Teruaki Hongo Department of Pediatrics Hamamatsu University School of Medicine 1-20-1 Handayama Hamamatsu Shizuoka 431-3192 Japan

Myoung-Ja Park Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Katsuyoshi Koh Gunma Children's Medical Center 779 Shimohakoda Kitatachibana Gunma 377-8577 Japan

Kohmei Ida Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Miyuki Kobayashi Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Junko Takita Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Tomohiko Taki Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

Hiroshi Yoshino Department of Pediatrics Kyorin University School of Medicine 6-20-2 Shinkawa Mitaka Tokyo 181-8611 Japan

Fumio Bessho Department of Pediatrics Kyorin University School of Medicine 6-20-2 Shinkawa Mitaka Tokyo 181-8611 Japan

Yasuhide Hayashi Department of Pediatrics, Graduate School of Medicine University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655 Japan

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Abstract

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.

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In vitro drug resistance to imatinib and mutation of ABL gene in childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia

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In vitro drug resistance to imatinib and mutation of ABL gene in childhood Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia

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