High incidence and unique features of antigen receptor gene rearrangements in TEL–AML1-positive leukemias

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Abstract
The t(12;21) translocation resulting in the TEL–AML1 gene fusion is found in 25% of childhood B-cell precursor (BCP) acute lymphoblastic leukemias (ALL). Since TEL–AML1 has been reported to induce cell cycle retardation and thus may influence somatic recombination, we analyzed 214 TEL–AML1-positive ALL by PCR for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) genes. As a control group, 174 childhood BCP ALL without a TEL–AML1 were used. The majority of TEL–AML1-positive leukemias had a higher number of Ig/TCR rearrangements than control ALL. They also had a more mature immunogenotype characterized by their high frequency of complete IGH, IGK-Kde, and TCRG rearrangements. While IGK-Kde and TCRG were more frequently rearranged on both alleles at higher age, IGH and TCRD rearrangements decreased in their incidence along with a decrease in biallelic IGH rearrangements. This suggests that the recombination process continues in these leukemias leading to ongoing rearrangements and possibly also deletions of antigen receptor genes. We here provide first evidence that somatic recombination of antigen receptor genes is affected by the TEL–AML1 fusion, and that further age-related differences are probably caused by the longer latency period of the prenatally initiated TEL–AML1-positive leukemias in older children.