Ohno Ryuzo
Aichi Cancer Center and Aichi Syukutoku University, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Int J Clin Oncol. 2006 Jun;11(3):176-83. doi: 10.1007/s10147-006-0582-5.
Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML). The translocation forms a chimeric gene, bcr-abl, which generates BCR-ABL. This fusion protein constitutively activate ABL tyrosine kinase and causes CML. Imatinib mesylate is a selective tyrosine kinase inhibitor on ABL, c-Kit and PGDF-receptor, and functions through competitive inhibition at the ATP-binding site of the enzyme, which leads to growth arrest or apoptosis in cells that express BCR-ABL. Imatinib has revolutionized the management of patients with CML, and at a dose of 400 mg daily has become the current standard therapy for newly diagnosed patients with CML even when they have HLA-matched family donors. Although imatinib therapy has only a 5-year history, it is hoped that CML will be cured with this drug and with forthcoming second-generation tyrosine kinase inhibitors as well as by allogeneic stem cell transplantation in patients who have become resistant to these drugs.
费城（Ph）染色体是慢性髓性白血病（CML）的细胞遗传学标志。这种易位形成了一个嵌合基因bcr-abl，它产生BCR-ABL。这种融合蛋白持续激活ABL酪氨酸激酶并导致CML。甲磺酸伊马替尼是一种针对ABL、c-Kit和血小板衍生生长因子受体（PGDF-受体）的选择性酪氨酸激酶抑制剂，通过在该酶的ATP结合位点进行竞争性抑制发挥作用，这会导致表达BCR-ABL的细胞生长停滞或凋亡。伊马替尼彻底改变了CML患者的治疗方式，即使新诊断的CML患者有人类白细胞抗原（HLA）匹配的家族供体，每天400毫克的剂量也已成为当前的标准治疗方案。尽管伊马替尼治疗仅有5年历史，但人们希望通过这种药物、即将出现的第二代酪氨酸激酶抑制剂以及对这些药物产生耐药性的患者进行异基因干细胞移植来治愈CML。
