Non-T, non-B acute lymphocytic leukemias: cellular origin based on molecular analyses of immunoglobulin and T-cell alpha- and beta-chain receptor gene rearrangements.

Fifteen non-T, non-B acute lymphocytic leukemia (ALL) cases were investigated for determining cellular origin based on molecular (immunoglobulin and T-cell alpha-receptor (TcR alpha) and T-cell beta-receptor (TcR beta) genes) and immunophenotypical analyses. As defined by monoclonal antibodies, they were classified into 2 groups; 12 cases as common ALL antigen (CALLA)-positive ALL and 3 cases as CALLA-negative ALL. Southern blot analysis revealed that 11 CALLA-positive ALL cases contained rearranged JH gene and 2 of them contained rearranged Jx genes, similar to recent views that most CALLA-positive leukemic cells are neoplastic B-cell precursors. One CALLA-positive ALL case, whose leukemic cells were also Leu-1 positive, showed no rearrangement of JH and TcR beta genes. On the other hand, non-T, non-B CALLA-negative ALL, so called null ALL, consisted of heterogenous groups with regard to lymphocyte differentiation and lineage; one out of 3 null ALL cases may be truely undifferentiated as shown neither JH nor TcR beta gene rearrangement, but other 2 cases showed either JH or TcR beta gene rearrangement. Dual rearrangements of Ig and TcR beta genes occur frequently in 3 out of 15 non-T, non-B ALL cases, but all cases of bigenotype showed no doubly marked profile and retained a completely fidelous immunophenotypic pattern. We further investigated the possibility that analysis of TcR alpha gene may be useful for determining cellular origin of non-T, non-B ALL leukemic cells.