|Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
STI571 is a specific inhibitor for BCR/ABL kinase, and has been used in a molecular target therapy for chronic myeloid leukemia (CML). In this study, we aimed to contribute to the establishment of the novel strategy for the treatment of CML by elucidating the molecular basis of the anti-leukemic action of STI571.
1)Molecular mechanisms of the anti-leukemic action of STI571: ARG is a tyrosine kinase closely related to ABL, which is oncogenic when fused to the transcriptional repressor ETV6. We found that leukemogenesis by an aberrant ARG kinase involves the suppression of p18/LNK4c, which is ubiquitously expressed and considered the major CKI in hematopoietic stem cells. STI571 can be an effective drug for the treatment of leukemias with deregulated ARG kinase activity.
2)Combination of STI571 with commonly-used anti-leukemic agents : We investigated the cytotoxic effects of STI571 on CML cells when combined with other anti-leukemic drugs. STI571 produced synergisity with IFN-α, and additive effects with hydroxyurea, cytarabine, homoharringtonine, doxorubicin, and etoposide. This result provides useful information to establish effective protocols for the treatment of CML.