A third tal-1 promoter is specifically used in human T cell leukemias.
A common feature of T cell acute lymphoblastic leukemias (T-ALLs) is the presence of structural alteration of the 5' part of the tal-1 locus, localized on chromosomal band 1p32. These alterations consist of either a t(1;14)(p32;q11) chromosomal translocation (3% of T-ALLs) or tald submicroscopic deletion (12-25% additional T-ALLs). We have characterized a case of T-ALL with t(1;14)(p32;q11) in which, unlike the majority of t(1;14), the recombination with the T cell receptor delta elements affected the 3' side of the tal-1 locus. In this case, tal-1 transcription is initiated from a promoter located within the fourth exon similarly to the DU 528 cell line. In a T-ALL bearing a t(1;14) affecting the 5' part of tal-1, two types of tal-1 transcripts were observed, namely those probably initiated from the D delta region juxtaposed to tal-1 by the translocation, and those from the exon 4 promoter. It is interesting that this exon 4 promotion was also found in leukemic T cell lines and T-ALL samples without apparent tal-1 genomic alteration. In contrast, no transcript initiated from the exon 4 promoter was found in T-ALL with tald1 or tald2 deletion. In these cells, tal-1 is expressed via SIL-tal-1 fused transcripts. Finally, this exon 4 initiation was detected neither in normal bone marrow, nor in malignant cells from the erythroid/megakaryocytic lineages. Taken as a whole, these data suggest that the exon 4 promoter is specifically active in T cell lineage.
Bernard
O
O
U. 301 Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Génétique Moléculaire (IGM), France.
Azogui
O
O
Lecointe
N
N
Mugneret
F
F
Berger
R
R
Larsen
C J
CJ
Mathieu-Mahul
D
D
D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002871:Chromosome Banding; D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D012326:RNA Splicing; D016372:RNA, Antisense / Q000138:chemical synthesis; D015183:Restriction Mapping; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D016372:RNA, Antisense; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human