Molecular characterization of Ph′+ hybrid acute leukemia

The configuration of the immunoglobulin heavy chain (IgH), T-cell receptor (TcR) β and γ chain regions, and the major breakpoint cluster region (M-bcr) genes were analysed in four cases of Ph′+ acute leukemia (AL). Monoclonal rearrangements of the IgH region were detected in three cases exhibiting two phenotypically distinct cell populations (i.e. one lymphoid and one myeloid). In one of these cases, identical genetic events were observed by molecular analysis of FACS separated blasts. Multi-lineage rearrangements involving also the TcR γ gene were observed in a biphenotypic AL showing co-expression of markers. The lack of rearrangements within the M-bcr gene, together with demonstration in one case of the Ph′+ AL specific p190 protein product, pointed against the occurrence of chronic myeloid leukemias presenting in blastic transformation. Our results imply that such cases are to be considered as true AL and should therefore be included in the definition of hybrid AL.