Two distinct mechanisms for the SCL gene activation in the t(1;14) translocation of T-cell leukemias.
Molecular study of a t(1;14)(p32;q11) translocation found in an acute T-cell leukemia (Kd cells) with a relatively mature phenotype is reported. Complex DNA rearrangements were characterized in the TCR alpha/delta locus. Besides a productive V alpha/J alpha assembly found on the normal allele, two deletions within the J alpha cluster were identified in the translocated allele. The translocation breakpoints involved the TCR delta gene on chromosome 14 and the SCL locus on chromosome band Ip32 that was recently shown to be activated by the t(1;14) translocation of the DU 528 leukemic cell line. Significantly, both Kd and DU 528 translocation breakpoints were located at the boundaries of D delta or J delta segments and were clustered in a 10 kb genomic fragment of the SCL gene. The presence of recombination signal motifs (heptamer-12/23 bp spacer-nonamer) on both normal chromosome partners, and N nucleotide addition on both derivative chromosomes involved the recombinase system in the translocation event. The SCL locus was highly expressed as a 5 kb transcript in Kd cells and, as already reported, as a 2 kb transcript in DU 528 cells. Importantly, a 5 kb SCL transcript was also detected in immature nonlymphoid hematopoietic cells but not in normal mature T cells, suggesting that it might correspond to the normal SCL transcript. Taken together, our data support the notion that the involvement of the SCL gene in the leukemogenic process may occur through overexpression of an apparently normal transcript (Kd cells) or expression of a truncated RNA (DU 528 cells).
Bernard
O
O
U301 INSERM CNRS, Institute de Génétique Moléculaire, France.
Guglielmi
P
P
Jonveaux
P
P
Cherif
D
D
Gisselbrecht
S
S
Mauchauffe
M
M
Berger
R
R
Larsen
C J
CJ
Mathieu-Mahul
D
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000648:ultrastructure*; D002883:Chromosomes, Human, Pair 14 / Q000648:ultrastructure*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015329:Gene Rearrangement, T-Lymphocyte; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006801:Humans; D019426:Integrases; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009857:Oncogenes; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D045522:Recombinases; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000737:chemistry
D051792:Basic Helix-Loop-Helix Proteins; D004254:DNA Nucleotidyltransferases; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D019426:Integrases; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D045522:Recombinases; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human; C115006:integron integrase IntI1