title: The 12;21 translocation involving TEL and deletion of the other TEL allele: two frequently associated alterations found in childhood acute lymphoblastic leukemia.
abstract: A recurrent t(12;21)(p13;q22) has recently been described in human acute lymphoblastic leukemias (ALLs). This translocation fuses TEL and AML1, two genes previously cloned from translocation breakpoints in myeloid leukemias. In addition, allelic loss of the TEL gene can be detected in 15% to 22% of childhood ALLs. In the present study, we have sought allelic deletions of TEL and the presence of the t(12;21) in 50 children with B-lineage ALL, using a combination of microsatellite typing, fluorescent in situ hybridization (FISH), and analysis of the fusion transcripts resulting from the TEL-AML1 gene fusion. Our results indicate that the association between the t(12;21) and the deletion of the nontranslocated allele of TEL is among the most frequent abnormalities observed in B-lineage ALLs. FISH analysis using several cosmid probes showed that, in one patient with a t(12;21) translocation involving TEL, the second allele had an intragenic deletion. This observation points to TEL as the actual target of 12p12-13 deletions in patients that associate a t(12;21) with a deletion. The TEL-AML1 fusion RNA was found in all patients with the t(12;21) whereas the reciprocal AML1-TEL transcript was only found in a subset of patients, suggesting that only the protein product encoded by TEL-AML1 is likely to play a role in leukemogenesis. The observation that, in two patients with the t(12;21), a deletion of TEL was only present in a subclone indicates that this deletion was a secondary event that occurred after the translocation. The frequent occurrence of TEL deletions in patients with t(12;21) suggests that the deletion of the normal TEL allele subsequent to the t(12;21) provides a further proliferative advantage to leukemic cells.
authors.affiliation: Laboratoire de Génétique Moléculaire des Cancers Humains, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Raynaud
authors.forename: H
authors.initials: H
authors.lastname: Cave
authors.forename: M
authors.initials: M
authors.lastname: Baens
authors.forename: C
authors.initials: C
authors.lastname: Bastard
authors.forename: V
authors.initials: V
authors.lastname: Cacheux
authors.forename: J
authors.initials: J
authors.lastname: Grosgeorge
authors.forename: C
authors.initials: C
authors.lastname: Guidal-Giroux
authors.forename: C
authors.initials: C
authors.lastname: Guo
authors.forename: E
authors.initials: E
authors.lastname: Vilmer
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: B
authors.initials: B
authors.lastname: Grandchamp
mesh_terms: D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human