以前的化疗研究几乎完全集中在细胞凋亡上。在这里，采用阿糖胞苷和伊达霉素的标准一线药物组合，在急性髓系白血病（AML）细胞系（n=3/10）、来自健康志愿者的外周血单个核细胞（n=10/10）和AML患者的原始细胞样本（n=18/39，法国-美国-英国亚型M4和M5）中诱导了特殊的caspase-独立、多(ADP-核糖)聚合酶1（PARP-1）介导的程序性细胞死亡“parthanatos”。在parthanatos阳性与阴性患者组中观察到生存率增加了3倍（风险比[HR]=0.28-0.37，p=0.002-0.046）。对parthanatos能力细胞中PARP-1活性的调控显示出基础PARP-1水平的细胞与PARP-1过表达或抑制的细胞相比具有更高的药物敏感性。RNA表达数据库中也观察到相同的趋势，支持PARP-1可能具有有利的化疗反应的最佳水平。版权所有© 2023作者。由Elsevier Inc.出版。保留所有权利。

Previous chemotherapy research has focused almost exclusively on apoptosis. Here, a standard frontline drug combination of cytarabine and idarubicin induces distinct features of caspase-independent, poly(ADP-ribose) polymerase 1 (PARP-1)-mediated programmed cell death "parthanatos" in acute myeloid leukemia (AML) cell lines (n = 3/10 tested), peripheral blood mononuclear cells from healthy human donors (n = 10/10 tested), and primary cell samples from patients with AML (n = 18/39 tested, French-American-British subtypes M4 and M5). A 3-fold improvement in survival rates is observed in the parthanatos-positive versus -negative patient groups (hazard ratio [HR] = 0.28-0.37, p = 0.002-0.046). Manipulation of PARP-1 activity in parthanatos-competent cells reveals higher drug sensitivity in cells that have basal PARP-1 levels as compared with those subjected to PARP-1 overexpression or suppression. The same trends are observed in RNA expression databases and support the conclusion that PARP-1 can have optimal levels for favorable chemotherapeutic responses.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.