title: SIL-TAL1 deletion in T-cell acute lymphoblastic leukemia.
abstract: The TAL1 gene on chromosome 1 encodes a hematopoietic transcription factor. Disruption of TAL1 via chromosomal translocation or a site-specific deletion has been reported in up to 30% of T-cell acute lymphoblastic leukemias (T-ALL). Here we used a polymerase chain reaction (PCR) assay to identify the 90 kb SIL-TAL1 deletion in a group of 19 cutaneous T-cell lymphomas and a series of 142 T-ALL patients (76 children, 66 adults). While none of the T-cell lymphoma exhibited a SIL-TAL1 recombination, seven T-ALL cases showed a type d1 and two patients a type d2 deletion. Of pediatric T-ALL, 9% (7/76) and of adult patients only 3% (2/66) were characterized by this genomic lesion. The deletion correlated with commitment to the T-cell receptor (TCR) alpha beta lineage, but lacked association with a distinct maturation stage. Sequence analysis of SIL-TAL1 breakpoints revealed marked heterogeneity at the junctional region among the nine patients due to random deletion and insertion of N-region nucleotides or templated P-nucleotide addition mediated via illegitimate V(D)J recombinase action. Clonospecific oligomer probes in conjunction with PCR allowed the detection of minimal residual disease in one out of four patients monitored during complete hematologic remission.
authors.affiliation: Department of Pediatrics II, University of Ulm, Germany.
authors.forename: J W
authors.initials: JW
authors.lastname: Janssen
authors.forename: W D
authors.initials: WD
authors.lastname: Ludwig
authors.forename: W
authors.initials: W
authors.lastname: Sterry
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human