TAS::75 0849::TAS TOPIC 255 DEVELOPMENT OF A TARGETED THERAPY FOR ACUTE MYELOID

急性髓系白血病(AML)是成人最常见的白血病之一，尽管研究取得了进展 在治疗中，成人患者的5年生存率不到20-50%，而老年人患者的5年生存率则明显降低。这个 在治疗AML的一种相对不常见的亚型--急性早幼粒细胞白血病--方面取得了显著的成功， 全反式维甲酸(ATRA)展示了具有更高疗效和更低毒性的药物的巨大前景。 利用ATRA，75-85%的患者有可能被推定治愈。ATRA的非凡成功源于 AML是一种以未成熟髓系细胞分化受阻为特征的疾病。 TRA通过迫使白血病细胞成熟来克服这种分化障碍。不幸的是，TRA做到了 临床上对90%-95%的AML患者无效。我们已经确定了治疗目标和优化的导联 针对这个靶点的化合物，导致AML患者分化诱导，而不是正常的 对全反式维甲酸的反应。在本申请中，我们将测试这种治疗急性髓系白血病的新型药物的临床实用性 小鼠模型系统。 提供密钥

Acute myeloid leukemia (AML) is one of the most common forms of leukemia in adults and despite advances in treatment the 5 year survival is less than 20-50% in adults and significantly lower in the elderly. The remarkable success in treating one relatively uncommon subset of AML, acute promyelocytic leukemia, with all trans-retinoic acid (ATRA) illustrates the great promise for agents with greater efficacy and less toxicity. Utilizing A TRA, the presumed cure of 75-85% of patients is possible. ATRA's remarkable success stems from the fact that AML is a disease characterized by the arrest of differentiation of immature myeloid cells. A TRA overcomes this block in differentiation by forcing leukemic cells to mature. Unfortunately A TRA does not work clinically for 90-95% of AML patients. We have identified a therapeutic target and an optimized lead compound against this target that leads to differentiation induction in AML patients that are not normally responsive to ATRA. In this application, we will test the clinical utility of this novel agent for AML using mouse model systems. Provide key