Chronic myeloid leukemic cells trigger poly(ADP-ribose) polymerase-dependent inactivation and cell death in lymphocytes

J Leukoc Biol. 2013 Jan;93(1):155-60. doi: 10.1189/jlb.0512257. Epub 2012 Oct 16.


NK cells and T cells are commonly dysfunctional in CML, and their status may determine the course of disease. We aimed to define the molecular mechanisms of leukemia-induced immunosuppression with focus on the role of ROS and the PARP-1 pathway of cell death. Malignant granulocytes from patients with BCR-ABL-positive CML expressed the oxygen radical-producing enzyme NOX, produced large amounts of ROS, and triggered extensive cell death in NK cells. Inhibition of PARP-1 maintained NK cell viability in cocultures with suppressive leukemic cells. Under conditions of oxidative stress, PARP-1 inhibition upheld the capacity of NK cells to kill myeloid leukemic cells, in addition to restoring the proliferation and cytokine production of NK cells and cytotoxic T cells. Our findings are suggestive of a novel pathway of relevance to immunosuppression in CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death
  • Coculture Techniques
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Oxidative Stress / immunology
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Reactive Oxygen Species
  • Poly(ADP-ribose) Polymerases