Quintas-Cardama Alfonso, Kantarjian Hagop, Jones Dan, Nicaise Claude, O'Brien Susan, Giles Francis, Talpaz Moshe, Cortes Jorge
Department of Leukemia, Unit 428, 1515 Holcombe Blvd, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Blood. 2007 Jan 15;109(2):497-9. doi: 10.1182/blood-2006-07-035493. Epub 2006 Sep 21.
Developing strategies to counteract imatinib resistance constitutes a challenge in chronic myelogenous leukemia (CML). Therapy with the tyrosine kinase inhibitors nilotinib (AMN107) and dasatinib (BMS-354825) has produced high rates of hematologic and cytogenetic response. Src kinase activation has been linked to Bcr-Abl-mediated leukemogenesis and CML progression. In addition to binding Abl kinase with less stringent conformational requirements than imatinib, dasatinib is a potent Src kinase inhibitor. In the current study, we report on 23 patients with CML (19 of them in accelerated or blastic phases) treated with dasatinib after treatment failure with both imatinib and nilotinib. More than half (13; 57%) of 23 patients responded to dasatinib: 10 (43%) had a complete hematologic response (CHR), including 7 (30%) who had a cytogenetic response (2 complete, 4 partial, and 1 minor). These results suggest that dasatinib may be active in some patients after failure with both imatinib and nilotinib.
制定对抗伊马替尼耐药性的策略是慢性粒细胞白血病（CML）治疗中的一项挑战。酪氨酸激酶抑制剂尼罗替尼（AMN107）和达沙替尼（BMS - 354825）治疗已产生高比例的血液学和细胞遗传学反应。Src激酶激活与Bcr - Abl介导的白血病发生及CML进展相关。除了以比伊马替尼更宽松的构象要求结合Abl激酶外，达沙替尼还是一种有效的Src激酶抑制剂。在本研究中，我们报告了23例CML患者（其中19例处于加速期或急变期），这些患者在伊马替尼和尼罗替尼治疗失败后接受了达沙替尼治疗。23例患者中超过半数（13例；57%）对达沙替尼有反应：10例（43%）获得完全血液学缓解（CHR），其中7例（30%）有细胞遗传学反应（2例完全缓解、4例部分缓解和1例微小缓解）。这些结果表明，达沙替尼在伊马替尼和尼罗替尼治疗失败后的部分患者中可能具有活性。
