Targeting NF-κB activation via pharmacologic inhibition of IKK2-induced apoptosis of human acute myeloid leukemia cells
Targeting NF-κB activation via pharmacologic inhibition of IKK2-induced apoptosis of human acute myeloid leukemia cells
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DOI：
10.1182/blood-2004-04-1463
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发表时间：
2005-01-15
期刊：
影响因子：
20.3
通讯作者：
Peyron, JF
中科院分区：
文献类型：
--
作者：
Frelin, C;Imbert, V;Peyron, JF
急性髓性白血病（AML）细胞的特征在于核因子-κ B（NF-κ B）转录因子的组成性和异常激活。这项对18名患者进行的体外研究表明，用特异性药理学抑制剂AS 602868靶向IKB激酶2（IKK 2）激酶以阻断NF-κ B活化，导致人原代AML细胞凋亡。此外，AS 602868增强了当前化疗药物多柔比星、阿糖胞苷或依托泊苷（VP 16）诱导的凋亡反应。AS 602868诱导的细胞死亡与线粒体跨膜电位的破裂和细胞半胱天冬酶的激活有关。NF-κ B抑制不影响正常的CD 34（+）造血前体细胞，这表明它可能是AML治疗的一种新的辅助策略。(C)2005年，美国血液学会。
Acute myeloid leukemia (AML) cells are characterized by a constitutive and abnormal activation of the nuclear factor-kappaB (NF-kappaB) transcription factor. This study, conducted in vitro on 18 patients, shows that targeting the IKB kinase 2 (IKK2) kinase with the specific pharmacologic inhibitor AS602868 to block NF-kappaB activation led to apoptosis of human primary AML cells. Moreover, AS602868 potentiated the apoptotic response induced by the current chemotherapeutic drugs doxorubicin, cytarabine, or etoposide (VP16). AS602868-induced cell death was associated with rupture of the mitochondrial transmembrane potential and activation of cellular caspases. NF-kappaB inhibition did not affect normal CD34(+) hematopoietic precursors, suggesting that it could represent a new adjuvant strategy for AML treatment. (C) 2005 by The American Society of Hematology.