Clinical relevance of immunophenotypic and immunogenotypic analysis in acute non-lymphoblastic leukaemia

Molecular biology is playing an increasing role in defining pathology today, and has clinical relevance in the routine work-up of patients with malignant diseases, especially those of the blood and lymphatic system. The majority of acute non-lymphoblastic leukaemias (ANLL) express specific myeloid differentiation markers and are terminal deoxynucleotidyl transferase (Tdt) negative. Rarely, some cases are Tdt+ and express the T-cell marker CD7. Although uncommon in Tdt-ANLL, there appears to be a significant incidence of T-cell receptor beta chain (TCR beta) and/or immunoglobulin heavy chain (IgH) gene rearrangements in Tdt+ ANLLs. We have investigated the immunogenotype of 39 patients with ANLL, including 28 from whom immunophenotypic data were available. Thirty-seven of 39 cases had germline IgH and TCR beta genes. Two cases, one with a myeloid/CD7+ CD2+ immunophenotype, had non-germline IgH gene arrangements detectable on Hind III digests only. The possibility of Hind III polymorphisms, or of true somatic gene rearrangement of the IgH gene in these patients, is discussed. Two additional cases had a Tdt+ CD7+ immunophenotype with germline IgH and TCR beta chain genes. Our results confirm the infrequent occurrence of IgH and TCR beta gene rearrangements in ANLL. Expression of Tdt and/or CD7, often in association with IgH gene rearrangements, would appear to identify a subgroup of ANLL patients that respond poorly to standard ANLL therapy and have a poorer prognosis. The diagnostic and prognostic importance of multiparametric analysis in ANLL is emphasised.