Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis
Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis
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DOI：
10.1182/blood-2011-11-391722
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发表时间：
2012-06-14
期刊：
影响因子：
20.3
通讯作者：
Martner, Anna
中科院分区：
文献类型：
--
作者：
Aurelius, Johan;Thoren, Fredrik B.;Martner, Anna
T细胞和自然杀伤(NK)细胞的功能障碍被认为是决定急性髓系白血病(AML)病程的指标，但关于淋巴细胞抑制的机制却知之甚少。我们的目的是评估人类恶性AML细胞在多大程度上使用NADPH氧化酶衍生的活性氧物种(ROS)作为一种免疫逃避策略。我们报道了在确诊时从未经治疗的AML患者的血液或骨髓中恢复的恶性单核细胞和单核细胞AML细胞亚群(分别为法-美-英[Fab]M4和M5)，表达NADPH氧化酶成分gp91(Phox)。高纯度的Fab M4/M5 AML细胞在激活时产生大量ROS，并在相邻的NK细胞、CD4(+)T细胞和CD8(+)T细胞中触发依赖聚[ADP-核糖]聚合酶-1的凋亡。相反，未成熟(FAb M1类)和成髓细胞(Fab M2类)AML细胞很少表达gp91(Phox)，不产生ROS，也不触发NK或T细胞凋亡。来自207例AML患者的微阵列数据证实，Fab-M4/M5 AML细胞比Fab-M1细胞(P<；10(-11))或Fab-M2细胞(P<；10(-9))表达更多的gp91(Phox)mRNA。我们的数据提示了一种单核细胞AML细胞逃避细胞免疫的新机制。(血。2012年；119(24)：5832-5837)
Dysfunction of T cells and natural killer (NK) cells has been proposed to determine the course of disease in acute myeloid leukemia (AML), but only limited information is available on the mechanisms of lymphocyte inhibition. We aimed to evaluate to what extent human malignant AML cells use NADPH oxidase-derived reactive oxygen species (ROS) as an immune evasion strategy. We report that a subset of malignant myelomonocytic and monocytic AML cells (French-American-British [FAB] classes M4 and M5, respectively), recovered from blood or BM of untreated AML patients at diagnosis, expressed the NADPH oxidase component gp91(phox). Highly purified FAB M4/M5 AML cells produced large amounts of ROS on activation and triggered poly-[ADP-ribose] polymerase-1-dependent apoptosis in adjacent NK cells, CD4(+) T cells, and CD8(+) T cells. In contrast, immature (FAB class M1) and myeloblastic (FAB class M2) AML cells rarely expressed gp91(phox), did not produce ROS, and did not trigger NK or T-cell apoptosis. Microarray data from 207 AML patients confirmed a greater expression of gp91(phox) mRNA by FAB-M4/M5 AML cells than FAB-M1 cells (P < 10(-11)) or FAB-M2 cells (P < 10(-9)). Our data are suggestive of a novel mechanism by which monocytic AML cells evade cell-mediated immunity. (Blood. 2012; 119(24):5832-5837)