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Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91(phox) expression and the PARP-1/PAR pathway of apoptosis.

Journal article
Authors Johan Aurelius
Fredrik Bergh Thorén
Aliasghar Akhiani
Mats Brune
Lars Palmqvist
Markus Hansson
Kristoffer Hellstrand
Anna Martner
Published in Blood
Volume 119
Issue 24
Pages 5832-7
ISSN 1528-0020
Publication year 2012
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine, Department of Microbiology and Immunology
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Biomedicine, Department of Infectious Medicine
Pages 5832-7
Language en
Links dx.doi.org/10.1182/blood-2011-11-39...
Keywords Adenosine Diphosphate Ribose, metabolism, Antigens, CD14, metabolism, Apoptosis, Bone Marrow, pathology, Cell Differentiation, immunology, Cell Line, Tumor, Flow Cytometry, Humans, Killer Cells, Natural, immunology, pathology, Leukemia, Myeloid, Acute, classification, enzymology, pathology, Lymphocyte Activation, immunology, Membrane Glycoproteins, metabolism, Monocytes, enzymology, immunology, pathology, Myeloid Cells, metabolism, pathology, NADPH Oxidase, metabolism, Poly(ADP-ribose) Polymerases, metabolism, Protein Subunits, metabolism, Reactive Oxygen Species, metabolism, Signal Transduction, T-Lymphocytes, enzymology, immunology, pathology
Subject categories Basic Medicine

Abstract

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.

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