p21Cip1 Confers resistance to imatinib in human chronic myeloid leukemia cells
p21Cip1 Confers resistance to imatinib in human chronic myeloid leukemia cells
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DOI：
10.1016/j.canlet.2009.11.017
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发表时间：
2010-06-01
期刊：
影响因子：
9.7
通讯作者：
Leon, Javier
中科院分区：
文献类型：
--
作者：
Ferrandiz, Nuria;Caraballo, Juan M.;Leon, Javier
伊马替尼是一种Bcr-Abl抑制剂，用作慢性粒细胞白血病（CML）的一线治疗。p21（Cip 1）最初被描述为细胞周期抑制剂，在某些模型中也保护免于凋亡。我们描述了伊马替尼下调CML细胞中p21（Cip 1）的表达。使用诱导型p21表达和瞬时转染的K562细胞，我们发现p21赋予伊马替尼诱导的凋亡的部分抗性。这种保护作用与p21引起的G2期阻滞、伊马替尼对Bcr-Abl的活性降低或p21的细胞质定位无关。结果表明p21（Cip 1）参与了CML患者对伊马替尼的反应。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Imatinib is a Bcr-Abl inhibitor used as first-line therapy of chronic myeloid leukemia (CML). p21(Cip1), initially described as a cell cycle inhibitor, also protects from apoptosis in some models. We describe that imatinib down-regulates p21(Cip1) expression in CML cells. Using K562 cells with inducible p21 expression and transient transfections we found that p21 confers partial resistance to imatinib-induced apoptosis. This protection is not related to the G2-arrest provoked by p21, a decrease in the imatinib activity against Bcr-Abl or a cytoplasmic localization of p21. The results suggest an involvement of p21(Cip1) in the response to imatinib in CML. (C) 2009 Elsevier Ireland Ltd. All rights reserved.