Clonal diversity, measured by heterogeneity of Ig and TCR gene rearrangements, in some acute leukaemias of childhood is associated with a more aggressive disease

Abstract

The pattern of immune system gene rearrangements in acute leukaemias of childhood is heterogeneous. The biological significance of this heterogeneity in childhood acute leukaemia is still poorly understood. In this study, we analysed 49 children with acute leukaemia (29 B-precursor acute lymphoblastic leukaemia (ALL), 5 relapsed cALL, 6 T-ALL, 7 acute non-lymphocytic (ANLL) and 2 mixed lineage leukaemias), for the presence of different immune system gene rearrangements (Ig JH, C kappa, C lambda, TCR J gamma, C beta, J delta and J alpha) by Southern blot hybridisation. The most prominent heterogeneity of immune system gene rearrangements was observed in the group of B-precursor ALL. The results from our study suggest that the heterogeneity of immune system gene rearrangement reflects clonal diversity in approximately one-third of patients with B-precursor ALL at presentation and in most patients in relapse. The observed association of clonal diversity with high white blood cell count, pre-B immunophenotype and age under 1 year in B-precursor ALL may have clinical significance. There was a significantly shorter disease-free survival in the group of B-precursor ALL patients with clonal diversity compared with those without clonal diversity. Clonal diversity may, therefore, be a mechanism of disease progression common to different types of aggressive B-precursor ALL.