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, Jeffrey S. Miller

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 γ (IFN-γ), or tumor necrosis factor α (TNF-α) 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.

Original languageEnglish (US)
Pages (from-to)3527-3533
Number of pages7
Issue number9
StatePublished - May 1 2003


Dive into the research topics of 'BCR/ABL alters the function of NK cells and the acquisition of killer immunoglobulin-like receptors (KIRs)'. Together they form a unique fingerprint.

Cite this