Simultaneous immunoglobulin/T-cell receptor gene rearrangements and multiclonality in childhood acute lymphoblastic leukemia

Twenty-five children less than 16 years of age with acute lymphoblastic leukemia (ALL) were investigated with immunologic, cytogenetic and molecular genetic techniques at diagnosis. All pre-B-cell ALL showed clonal rearrangements in the immunoglobulin heavy chain gene (J_H and/or Cμ). A very high proportion of the pre-B-cell leukemias (17 of 23 cases) also snowed clonal rearrangements in T-cell receptor genes (Tγ and/or Tβ). The two T-cell leukemias exhibited clonal T-cell receptor gene rearrangements and in one Jh and kappa light chain rearrangments also. The T-cell receptor gene rearrangements found in pre-B-cell leukemias appeared to occur randomly with respect to the Tβ and Tγ genes. A significant proportion of the leukemias (at least 24%) seemed to harbor more than one malignant (sub)clone at diagnosis. Cytogenetic studies revealed a clonal abnormality in 10 cases. Only 2 showed hyperdiploidy (> 50 chromosomes). The only correlation between cytogenetic findings and rearrangement patterns was extra bands corresponding to a possible trisomy of chromosome 14. Our data indicate, in line with previous studies, that childhood ALL has complex rearrangement patterns not useful for lineage sub-classification. For this purpose immunophenotyping appears to be superior. However, molecular analysis can reveal the presence of more than one clone not detected by immunophenotyping or karyotyping, and distribution of clones in different compartments. In this study no correlation with clinical outcome was observed.