title: TEL/AML1-positive patients lacking TEL exon 5 resemble canonical TEL/AML1 cases.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: CLIP, Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic. marketa.zaliova@lfmotol.cuni.cz
authors.forename: Marketa
authors.initials: M
authors.lastname: Zaliova
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
authors.forename: Martina
authors.initials: M
authors.lastname: Vaskova
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Jan
authors.initials: J
authors.lastname: Zuna
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C102421:TEL-AML1 fusion protein