MYELOID NEOPLASIA Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis
نویسندگان
چکیده
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-AmericanBritish [FAB] classes M4 and M5, respectively), recovered from blood or BM of untreated AML patients at diagnosis, expressed the NADPH oxidase component gp91phox. Highly purified FAB M4/M5 AML cells produced large amounts of ROS on activation and triggered poly-[ADPribose] 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 gp91phox, did not produce ROS, and did not trigger NK or T-cell apoptosis. Microarray data from 207 AML patients confirmed a greater expression of gp91phox mRNA by FABM4/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)
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