The detection of clonal proliferation in granular lymphocyte‐proliferative disorders of natural killer cell lineage

Abstract
Summary. The clonal proliferation of large granular lymphocytes can be detected in patients with T‐cell‐lineage granular lymphocyte‐proliferative disorders (T‐GLPD) by Southern blotting T‐cell receptor genes. However, this cannot be applied to patients with natural killer‐cell‐lineage GLPD (NK‐GLPD) as it lacks a clonal marker. We therefore investigated the use of two other diagnostic techniques in evaluating clonal proliferation in Japanese patients with NK‐GLPD (n = 4) and T‐GLPD (n=3) by chromosomal analysis of peripheral blood mononuclear cells (PBMC) stimulated with either interleukin‐2 or phytohaemaggluti‐nin, and Epstein‐Barr viral (EBV) genomic DNA analysis. Chromosomal analysis revealed abnormal karyotypes in the PBMC of three of four patients with NK‐GLPD, whereas EBV analysis showed a monoclonal terminal configuration in the PBMC in the fourth patient. Southern blots revealed rearrangements of the TCR genes in all three patients with T‐GLPD but in none of those with NK‐GLPD. It is suggested that these methods may be useful in detecting the abnormal proliferation of large granular lymphocytes in NK‐GLPD.