Abnormalities of antigen receptor gene rearrangements in human B-lineage acute lymphoblastic leukemias

In this short review, we analyse some recent data describing T-cell receptor gene rearrangement abnormalities occurring specifically in B-lineage ALLs. Numerous studies have shown that the lineage specificity of TCR gene rearrangements is lacking in malignant pre-B cells. The resulting inappropriate TCR gene recombinations use the recombinase machinery common to normal B and T cells and, with the exception of the TCRb locus, are similar to gene rearrangements associated with early stages of T-cell ontogeny. In most cases, these rearrangements are not efficiently transcribed. There is no clear selection for in-frame recombinations. As these rearrangements are clonal and found in all tumor cells, it may be hypothesized that they may reflect some cellular dysfunctions contemporary of the initiation of transformation before the step of clonal expansion. We favor the hypothesis that inappropriate rearrangements are due to a defective control of germline TCR gene segment transcription. This defect may reflect a more severe transcriptional dysregulation potentially involved in some alterations of cell phenotype and more generally in ALL oncogenesis.