Abstrakt
Background. The TEL/AML1 fusion gene which represents the most frequent genetic abnormality in childhood ALL, usually results from genomic breakpoints in TEL intron 5 and AML1 intron 1 or 2.
At the protein level, the helix loop helix domain and exon 5-coded central region of TEL are typically fused to almost entire AML1 including DNA-binding domain. Procedure.
We identified two ALL patients with genomic breakpoints within TEL intron 4 resulting in variant TEL/AML1 fusion lacking the TEL exon 5-coded central region. This region was supposed to play an important role in TEL/AML1 function, particularly in TEL/AML1-mediated transcriptional repression of AML1 targets.
We aimed at investigating the impact of the loss of this region on disease behavior and TEL/AML1 function. We compared clinical and biological characteristics, treatment response, and outcome of the variant versus classical TEL/AML1 cases, analyzed genome wide gene expression profiles and performed reporter gene assay.
Results. No distinct differences between variant and classical TEL/AML1 cases were observed including gene expression profiling and detailed immunophenotyping.
By using reporter gene assay, we showed that the loss of the central region does not influence the TEL/AML1-mediated transcriptional repression. Conclusions.
The deletion of the central region did not affect the TEL/AML1-specific phenotype; we did not find any relevant differences in clinical and biological features when variant versus classical TEL/AML1-positive cases were compared. Thus, our data does not support hypothesis that the central region of TEL is indispensable for TEL/AML1 driven leukemogenesis.