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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-04-1172.
Submitted April 18, 2002
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA * Corresponding author; email: mille011{at}tc.umn.edu.
NK cells decrease in function during 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 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, IFN-
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| Copyright © 2003 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
or TNF-
production. Although the ABL-specific tyrosine kinase inhibitor 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 (KIR). Unlike the decreased natural cytotoxicity, the function of the activating CD158j receptor remained intact. Southern blotting and hybridization with an eGFP probe show 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.
