抗凋亡蛋白 Mcl-1 对于急性髓系白血病的发生和持续生长是必需的。
Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia.
机构信息
The Walter and Eliza Hall Institute, Parkville, Melbourne, Victoria 3052, Australia.
出版信息
Genes Dev. 2012 Jan 15;26(2):120-5. doi: 10.1101/gad.182980.111.
Abstract
Acute myeloid leukemia (AML) frequently relapses after initial treatment. Drug resistance in AML has been attributed to high levels of the anti-apoptotic Bcl-2 family members Bcl-x(L) and Mcl-1. Here we report that removal of Mcl-1, but not loss or pharmacological blockade of Bcl-x(L), Bcl-2, or Bcl-w, caused the death of transformed AML and could cure disease in AML-afflicted mice. Enforced expression of selective inhibitors of prosurvival Bcl-2 family members revealed that Mcl-1 is critical for survival of human AML cells. Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML.
摘要
急性髓系白血病（AML）在初始治疗后经常复发。AML 中的耐药性归因于高水平的抗凋亡 Bcl-2 家族成员 Bcl-x(L)和 Mcl-1。在这里，我们报告说，去除 Mcl-1，但不是缺失或药理学阻断 Bcl-x(L)、Bcl-2 或 Bcl-w，会导致转化的 AML 死亡，并可能治愈 AML 小鼠的疾病。对选择性存活 Bcl-2 家族成员抑制剂的强制表达表明，Mcl-1 对人类 AML 细胞的存活至关重要。因此，针对 Mcl-1 或其表达调节剂可能是治疗 AML 的一种有用策略。
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