AbstractBackgroundThe 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.ProcedureWe 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.ResultsNo 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.ConclusionsThe 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. Pediatr Blood Cancer 2011;56:217–225. © 2010 Wiley‐Liss, Inc.