Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status

The large majority of childhood B-precursor cell acute lymphoblastic leukaemia cases present IgH and TCRδ gene rearrangements. These rearrangements have been widely used as specific markers for monitoring minimal residual disease. However, their prognostic value still remains unclear. In order to determine whether IgH and TCRδ gene rearrangements have any influence on relapse and event-free survival (EFS), we analysed the clinical impact of these genetic characteristics in 51 B-precursor acute lymphoblastic leukaemia patients. 46/51 patients (90.2%) showed IgH gene rearrangements by Southern blot and/or polymerase chain reaction (PCR) analysis. No statistically significant associations were found between IgH gene rearrangement pattern and age, sex, WBC count, immunophenotype, risk factor, relapse or EFS. 27/41 patients (66%) showed Vδ₂Dδ₃ recombination by Southern blot and/or PCR analysis. At a median follow-up of 53 months the estimated 5-year EFS probability was 78 ± 3% for the whole group. The EFS probability among patients with a Vδ₂Dδ₃ recombination pattern in the TCRδ locus was 90 ± 3%, whereas for patients without Vδ₂Dδ₃ recombination was 39 ± 13% ( P  < 0.005).
IgH rearrangement patterns do not appear to influence relapse or EFS probability. However, TCRδ gene rearrangement patterns have a relevant impact on the relapse rate and the EFS probability. Patients with Vδ₂Dδ₃ recombination have better clinical outcome than patients without this recombination, independent of any other prognostic factors.