Genotypic characterization of common acute lymphoblastic leukemia may improve the phenotypic classification

Abstract

The reactivity of five anti-B monoclonal antibodies (McAb)-OKB2 (CD24), B4 (CD19), Leu12 (CD19), BA1 (CD24), B1 (CD20)--as well as the presence of cytoplasmic immunoglobulins (CyIg) were assessed in 100 cases of common acute lymphoblastic leukemia (cALL) at presentation (TdT+, J5 [CD10]+, HLA-Dr+). All cases studied revealed one or more B-cell related markers and a hierarchy in their expression was documented: OKB2 was positive in all cases tested (100%), B4 was expressed in 96.4% of cases, Leu12 in 95.8%, BA1 in 94.9%, B1 in 18.3%, and CyIg in 23%. Further evidence of the B-cell origin of cALL was obtained by molecular analyses at the DNA level which demonstrated the presence of an Ig heavy chain gene rearrangement in all 37 cases assessed, while 37.8% showed a light chain gene reorganization. A genomic subclassification of cALL demonstrated that the majority of cases showed an immature molecular configuration with one (8.1%) or both (54.1%) Ig heavy chain alleles rearranged and a germ-line configuration of the light chain genes; 27% revealed a heavy chain gene involvement and one k allele rearranged. Only four cases (10.8%) showed a more mature configuration with both k alleles rearranged or a gamma chain gene involvement. This study confirms that cALL is characterized by the proliferation of immature B-lineage-committed elements and indicates that the leukemic cells are blocked at different levels of B-differentiation which may be recognized with the use of multiple phenotypic or genotypic B-cell-related markers.