KHYG-1 Cells

KHYG-1 is a human natural killer (NK) cell leukemia cell line established from the peripheral blood of an adult female patient diagnosed with aggressive NK-cell leukemia. The cell line was derived at initial diagnosis and represents an Epstein-Barr virus (EBV)-negative NK-cell malignancy, distinguishing it from many NK/T-cell lymphoma models that are EBV-associated. KHYG-1 cells grow in suspension and display the cytomorphologic and immunophenotypic characteristics of activated NK cells, including expression of CD56 and cytoplasmic CD3ε, while lacking surface CD3 and T-cell receptor gene rearrangements, consistent with true NK-cell lineage derivation.

Molecular profiling studies have included KHYG-1 in genomic and transcriptomic analyses of NK-cell malignancies. Array comparative genomic hybridization and gene expression studies across NK-cell lines have identified recurrent chromosomal abnormalities in NK-cell tumors, such as deletions involving 6q21 and alterations affecting tumor suppressor pathways. In contrast to several EBV-positive NK-cell lines, KHYG-1 does not harbor detectable ATR gene alterations in analyses of the full coding region, underscoring molecular heterogeneity within NK-cell neoplasms. Gene expression profiling places KHYG-1 within the NK-cell lineage cluster, characterized by expression of NK-associated receptors and cytotoxic effector molecules, and distinct from cytotoxic αβ and γδ T-cell lymphomas.

Functionally, KHYG-1 exhibits interleukin-2-dependent proliferation in vitro and retains cytotoxic activity typical of NK cells. The line has been widely used to investigate signaling pathways critical to NK-cell survival and proliferation, including aurora kinase A and NOTCH pathway components, as well as to evaluate candidate therapeutic inhibitors targeting NK-cell malignancies. As an EBV-negative model of aggressive NK-cell leukemia, KHYG-1 provides a valuable in vitro system for studying intrinsic oncogenic mechanisms in NK-cell transformation, independent of viral-driven lymphomagenesis.