title: Does activation of the TAL1 gene occur in a majority of patients with T-cell acute lymphoblastic leukemia? A pediatric oncology group study.
abstract: Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene. Although TAL1 expression has not been observed in normal lymphocytes, TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele. Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL. In this report, we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL, including many that do not display an apparent TAL1 gene alteration. A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells. Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement. In the leukemic cells of patients without detectable TAL1 rearrangements, TAL1 transcription occurred in either a monoallelic (3 of 7 patients) or a biallelic (4 of 7 patients) fashion. Thus, TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences (affecting expression of a single TAL1 allele) or changes in trans-acting factors that control TAL1 transcription (affecting expression of both TAL1 alleles).
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9048, USA.
authors.forename: R O
authors.initials: RO
authors.lastname: Bash
authors.forename: S
authors.initials: S
authors.lastname: Hall
authors.forename: C F
authors.initials: CF
authors.lastname: Timmons
authors.forename: W M
authors.initials: WM
authors.lastname: Crist
authors.forename: M
authors.initials: M
authors.lastname: Amylon
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Baer
mesh_terms: D000483:Alleles; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D001853:Bone Marrow / Q000473:pathology; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology; D002648:Child; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D015321:Gene Rearrangement; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010996:Pleural Effusion / Q000473:pathology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human