Molecular characterization of illegitimate TCRδ gene rearrangements in acute myeloid leukaemia

SUMMARY. Recently, we and others have shown the occurrence of TCRδ gene rearrangements in acute myeloid leukaemia (AML). In this study we describe the molecular characteristics of these rearrangements by the polymerase chain reaction (PCR) and the direct sequencing of PCR products. 11 rearrangements were characterized in blast cell samples from six patients. We found a heterogenous pattern of TCRδ gene rearrangements with involvement of Vδ1-5 regions. These findings differ from observations in T-ALL and B-cell precursor ALL, where predominantly usage of Vδ1 and Vδ2 regions has been described. Furthermore, extensive diversity of junctional sites was observed, including addition of up to 37 N nucleotides, nucleotide deletions at junction sites of Vδ and Jδ segments and usage of up to three Dδ segments. The Dδ3 fragment was the most frequently used diversity element and was found in 10 rearrangements. Nine of the 11 rearrangements were non-functional, either incomplete or out of the reading frame. Therefore a functional TCRδ cannot be expressed in these myeloid blast cells.