A new human natural killer leukemia cell line, IMC-1. A complex chromosomal rearrangement defined by spectral karyotyping: functional and cytogenetic characterization

Abstract

A new human IL-2 dependent leukemic cell line with a natural killer (NK) cell phenotype, IMC-1, was established from an adult patient with aggressive NK cell leukemia. The IMC-1 cell line expresses the CD56, CD2, CD11a, CD38 and HLA-DR cell surface antigens, whereas the CD16 and CD8 antigens expressed on the primary leukemic blasts from which the cell line was derived were lost after 7 and 28 weeks of culture, respectively. The IMC-1 cell line displays functional NK cytotoxicity and lyses target cells in a non-MHC restricted, antibody-independent manner with equal or superior efficiency to freshly isolated NK cells. Cytogenetic analysis at presentation and after 55 weeks in culture revealed complex structural and numerical abnormalities, defined by classic G-banding and by spectral karyotyping (SKY). Three apparently intact copies of chromosome 8 occurred in the diagnostic bone marrow specimen; the cell line also contains three copies of chromosome 8 but each was structurally altered. The development and detailed characterization of this new NK leukemic cell line will facilitate biologic and functional studies of NK cells and chromosomal aberrations potentially important in leukemic transformation.

Introduction

Natural killer (NK) cells are defined not only by their ability to lyse target cells in a non-MHC restricted manner but also by the expression of a variety of cell surface markers, most of which are also expressed by either myeloid or T cells [1], [2], [3]. NK cells are characterized by expression of CD56—a variantly spliced form of the neural cell adhesion molecule (NCAM), and CD16, the low affinity IgG F_cyIII receptor which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). Additional antigens frequently expressed include CD11a (LFA), CD11b (the C3bi receptor), and the T cell-associated antigens CD2, CD7, low levels of CD8, and CD38. There is considerable immunophenotypic overlap between NK and cytotoxic T cells, cells expressing CD3 and/or the T cell receptor (TCR), C cells with clonal rearrangements of TCR genes are more appropriately considered T cell-derived and are excluded from the NK cell lineage. Several NK cell lines have been reported [4], [5], [6], [7], [8], [9]. The operational definition of these NK cell lines from NK cell malignancies includes a CD2⁺, CD3⁻, CD16⁻, C56⁺ phenotype with TCR genes in the germ line. The morphology shows azurophilic granules and large cells. In addition these lines are IL-2 dependent and some are Epstein–Barr virus (EBV) positive. At least one of the cell lines (KHYG-1) demonstrated a point mutation in exon 7 of the p53 gene [6]. These NK lines all show NK activity with karyotype numerical and structural alterations [5]. Two NK-like T-cell lines (DERL-2 and DERL-7) were both near-diploid with iso-7q [7]. Another NK cell line, NK-92, contains complex chromosomal rearrangements that include changes in chromosomes 8 and 12 [9]. We report the establishment of a new leukemic cell line, IMC-1, which has maintained functional and immunophenotypic characteristics of true NK cells for over 10 years.