PARP1-driven apoptosis in chronic lymphocytic leukemia.
PARP1-driven apoptosis in chronic lymphocytic leukemia.
复制标题
慢性淋巴细胞性白血病中的PARP1驱动凋亡。
DOI：
10.1155/2014/106713
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发表时间：
2014
影响因子：
--
通讯作者：
Viniou NA
中科院分区：
文献类型：
--
作者：
Diamantopoulos PT;Sofotasiou M;Papadopoulou V;Polonyfi K;Iliakis T;Viniou NA
慢性淋巴细胞白血病（CLL）被认为是一种恶性肿瘤，导致细胞凋亡的缺陷。因此，靶向CLL中的凋亡途径可能对其管理有价值。聚[ADP-核糖]聚合酶1（Poly [ADP-ribose] polymerase 1，PARP 1）是一个作为DNA损伤传感器的核酶家族的主要成员。通过结合DNA受损结构，PARP 1招募修复酶并作为存活因子，但如果损伤足够严重，其作用可能导致细胞通过caspase激活或坏死而凋亡。我们测量了26例CLL患者的PARP 1 mRNA和蛋白预处理水平，以及15例接受3个周期免疫化疗后的患者和15例健康献血员的相应治疗后水平。治疗前和治疗后的PARP 1水平之间没有差异，但我们发现治疗后样本中被半胱天冬酶切割的PARP 1的89 kDa片段的统计学显著相对增加，表明治疗后CLL患者中与PARP 1相关的细胞凋亡。我们的研究结果是该领域的重要一步，特别是在PARP 1抑制剂时代，并可能作为未来CLL中这些药物临床试验的基础。
Chronic lymphocytic leukemia (CLL) is considered a malignancy resulting from defects in apoptosis. For this reason, targeting apoptotic pathways in CLL may be valuable for its management. Poly [ADP-ribose] polymerase 1 (PARP1) is the main member of a family of nuclear enzymes that act as DNA damage sensors. Through binding on DNA damaged structures, PARP1 recruits repair enzymes and serves as a survival factor, but if the damage is severe enough, its action may lead the cell to apoptosis through caspase activation, or necrosis. We measured the PARP1 mRNA and protein pretreatment levels in 26 patients with CLL and the corresponding posttreatment levels in 15 patients after 3 cycles of immunochemotherapy, as well as in 15 healthy blood donors. No difference was found between the pre- and posttreatment levels of PARP1, but we found a statistically significant relative increase of the 89 kDa fragment of PARP1 that is cleaved by caspases in the posttreatment samples, indicating PARP1-related apoptosis in CLL patients after treatment. Our findings constitute an important step in the field, especially in the era of PARP1 inhibitors, and may serve as a base for future clinical trials with these agents in CLL.
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DOI：
10.1186/1478-811x-8-31
发表时间：
2010-12-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Chaitanya GV;Steven AJ;Babu PP
通讯作者：
Babu PP
DOI：
10.1006/bbrc.2001.4985
发表时间：
2001-06-08
影响因子：
3.1
作者：
Oei, SL;Shi, Y
通讯作者：
Shi, Y
影响因子：
4.2
作者：
Ying, WH;Alano, CC;Swanson, RA
通讯作者：
Swanson, RA
影响因子：
16
作者：
Krishnakumar R;Kraus WL
通讯作者：
Kraus WL
影响因子：
4.8
作者：
Margolin, N;Raybuck, SA;Livingston, DJ
通讯作者：
Livingston, DJ