title: Two site-specific deletions and t(1;14) translocation restricted to human T-cell acute leukemias disrupt the 5' part of the tal-1 gene.
abstract: Analysis of several cases of t(1:14)(p32;q11) translocation present in 3% of T-cell acute leukemias (T-ALL) has revealed the tal-1 gene. This gene encodes a helix-loop-helix protein. It has been found to be expressed in normal bone marrow and in leukemic T-cell and erythroleukemia cell lines, but not in normal T cells. Recently, a site-specific deletion, tald, renamed tald1 in this paper, has been detected in a high proportion of pediatric T-ALL, which arose by a site-specific DNA recombination between tal-1 and a new locus termed SIL. In this study we searched for structural rearrangements within tal-1 in a panel of 134 non-selected leukemic patients (including 66 with T-ALL). Only 6% of patients with T-ALL harbored the tald1 deletion. A second specific deletion termed tald2 was observed in another 6% of T-ALL patients; it involves another site within tal-1 plus the same site as tald1 in the SIL locus. Similarly to tald1 deletion, tald2 junctions harbor structural characteristics that are reminiscent of aberrant recombinase activity. Moreover, we report a detailed analysis of the tal-1 gene structure. Transcription analysis and in vitro translation data are consistent with the differential expression of several TAL-1 protein species containing the HLH motif but differing in their amino terminus. Taken together, our data indicate that t(1;14) translocations and both tald deletions disrupt the 5' part of the tal-1 gene, placing its entire coding sequences under the control of the regulatory elements of the TCR-delta gene or the SIL gene, both of which are normally expressed in T-cell lineage.
authors.affiliation: INSERM U301, Institut de Génétique Moléculaire, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Bernard
authors.forename: N
authors.initials: N
authors.lastname: Lecointe
authors.forename: P
authors.initials: P
authors.lastname: Jonveaux
authors.forename: M
authors.initials: M
authors.lastname: Souyri
authors.forename: M
authors.initials: M
authors.lastname: Mauchauffé
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: C J
authors.initials: CJ
authors.lastname: Larsen
authors.forename: D
authors.initials: D
authors.lastname: Mathieu-Mahul
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005809:Genes, Regulator / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D011948:Receptors, Antigen, T-Cell