Cross-lineage rearrangement of antigen receptor genes in atypical chronic myeloid leukemia.

The configuration of immunoglobulin (Ig) and T-cell receptor (TCR) genes was investigated in a case of atypical chronic myeloid leukemia (aCML) lacking a cytogenetically detectable Philadelphia chromosome and molecular evidence of breakpoint cluster region (bcr) rearrangement as determined by 5' and 3' bcr gene probes. Dual clonal rearrangement of Ig-heavy (H) and TCR-delta chain genes was identified. The genes for TCR-gamma and beta chain as well as Ig-kappa (k) chain were in germline configuration. These findings indicate transformation to have occurred in a hemopoietic stem cell with the capacity for antigen receptor gene rearrangement. The demonstration of cross-lineage rearrangement of both Ig and TCR genes lends support to evidence from G6PD alloenzyme studies that the target of transformation in aCML is an early stem cell not yet irreversibly committed to myeloid differentiation. Further studies are indicated to ascertain whether antigen receptor gene rearrangement constitutes a molecular marker useful in the diagnosis of aCML.