Immunoglobulin heavy chain and T-cell receptor gamma and beta chain gene rearrangements in acute myeloid leukemias.

Somatic rearrangements of immunoglobulin (Ig) and T-cell receptor (TCR) genes are the basis for the production of receptors for antigen in B-cells and T-cells, respectively. Here, we have studied the extent and pattern of rearrangements at Ig and TCR loci in 17 patients presenting with acute myeloid leukemia (AML). Our data demonstrate illegitimate clonal rearrangements at Ig heavy and/or TCR beta chain genes in 5 of 17 AML patients. In four of these five patients, rearrangements at the TCR beta chain gene locus were also observed. Seven patients displayed clonal TCR gamma chain gene rearrangements as the only abnormality. Rearrangements at Ig light chain and TCR alpha chain gene loci were not detected. Illegitimate TCR gamma chain gene rearrangements in AML involve recombinations of only a subset of V gamma genes, predominantly with the J gamma 1 region. Rearrangements at the TCR beta chain gene locus are characterized by both D-J and V-D-J recombinations, with predominant use of the J beta 1 region. The absence or presence of illegitimate antigen receptor gene rearrangements in AML may constitute a prognostic marker. In addition, these alterations can be used to establish clonality in AML with direct applications in the monitoring of disease. Finally, the present data relate to the problem of lineage assignment of acute leukemias based on Ig and TCR gene rearrangements and strongly suggest that the latter cannot be regarded as unequivocal evidence for the B-cell or T-cell lineage, respectively.