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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-04-1172.
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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3527-3533
IMMUNOBIOLOGY
BCR/ABL alters the function of NK cells and the
acquisition of killer immunoglobulin-like receptors
(KIRs)
Elena G. Chiorean,
Scott J. Dylla,
Krista Olsen,
Todd Lenvik,
Yvette Soignier, and
Jeffrey S. Miller
From the Division of Hematology-Oncology and
Transplantation, University of Minnesota Cancer Center,
Minneapolis.
Natural killer (NK) cells decrease in function during chronic
myelogenous leukemia (CML) progression from chronic phase to blast
crisis, and they can become
BCR/ABL+ late in
the disease course. To study this altered function, NK92 cells were
transduced with the BCR/ABL oncogene. In contrast
to the parental cells, which died when deprived of interleukin
2 (IL-2), p210+ NK92 cells proliferated and
survived indefinitely in the absence of IL-2. BCR/ABL also
decreased the natural cytotoxicity of NK92 cells against K562 targets,
without affecting IL-2, interferon  (IFN-), or tumor
necrosis factor  (TNF-) production. Although the ABL-specific
tyrosine kinase inhibitor imatinib mesylate (STI-571) had no
effect on parental NK92 cells, it markedly decreased the growth and
survival of IL-2-independent p210+ NK92 cells. In contrast
to the parental cell line, serial analysis of p210+ NK92
cells detected small populations that clonally expressed one or more
killer immunoglobulin-like receptors (KIRs). Unlike the decreased
natural cytotoxicity, the function of the activating CD158j receptor
remained intact. Southern blotting and hybridization with an enhanced
green fluorescence protein (eGFP) probe showed that
KIR and KIR+ NK92 cells were all derived from
the same clone, suggesting that KIR acquisition remains dynamic at the
maturational stage represented by the NK92 cell line. When tested in
primary CD56+bright NK cells, p210 induced partial
IL-2-independent growth and increased KIR expression similar to
findings in NK92 cells. This is the first study to show that
BCR/ABL, well known for its effects on the myeloid lineage,
can alter the function of lymphoid cells, which may be associated with
the defect in innate immunity associated with CML progression.
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M. Terme, C. Borg, F. Guilhot, C. Masurier, C. Flament, E. F. Wagner, S. Caillat-Zucman, A. Bernheim, A. G. Turhan, A. Caignard, et al.
BCR/ABL Promotes Dendritic Cell-Mediated Natural Killer Cell Activation
Cancer Res.,
July 15, 2005;
65(14):
6409 - 6417.
[Abstract]
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