Advanced

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

Aurelius, Johan; Thoren, Fredrik B.; Akhiani, Ali A.; Brune, Mats; Palmqvist, Lars; Hansson, Markus LU ; Hellstrand, Kristoffer and Martner, Anna (2012) In Blood 119(24). p.5832-5837
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]... (More)
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) (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
119
issue
24
pages
5832 - 5837
publisher
American Society of Hematology
external identifiers
  • wos:000307396500036
  • scopus:84862490496
ISSN
1528-0020
DOI
10.1182/blood-2011-11-391722
language
English
LU publication?
yes
id
722252d9-127f-4c48-bbb1-3bda26174995 (old id 3073390)
date added to LUP
2012-10-05 07:13:17
date last changed
2017-10-29 03:16:40
@article{722252d9-127f-4c48-bbb1-3bda26174995,
  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 &lt; 10(-11)) or FAB-M2 cells (P &lt; 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)},
  author       = {Aurelius, Johan and Thoren, Fredrik B. and Akhiani, Ali A. and Brune, Mats and Palmqvist, Lars and Hansson, Markus and Hellstrand, Kristoffer and Martner, Anna},
  issn         = {1528-0020},
  language     = {eng},
  number       = {24},
  pages        = {5832--5837},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91(phox) expression and the PARP-1/PAR pathway of apoptosis},
  url          = {http://dx.doi.org/10.1182/blood-2011-11-391722},
  volume       = {119},
  year         = {2012},
}