Involvement of the TCL5 gene on human chromosome 1 in T-cell leukemia and melanoma.

Abstract

We analyzed a t(1;14)(p32;qll) chromosomal translocation in a human lymphohemopoietic stem cell line derived from a patient with acute T-lymphoblastic leukemia.The chromosomal joining on the lp+ chromosome occurred at the T-cell receptor 8 diversity (D82) segment, and the reciprocal chromosomal joining on the 14q-chromosome occurred at the T-cell 8 diversity segment D8,. The involvement of 8 diversity segments at the translocation junctions suggests that the translocation occurred during an attempt at DS1-DS2 joining in a stem cell. The segment of chromosome 1 at band p32, adjacent to the chromosomal breakpoint, encodes a transcriptional unit designated TCLS (T-cell leukemia/lymphoma 5). The differential expression of the TCL5 RNA transcripts in this lymphohemopoietic stem cell line relative to several other T-and B-cell lines suggests that TCL5 gene expression is an integral event in the pathogenesis of the T-cell leukemia. Rearrangement of the TCL5 locus in a human melanoma cell line carrying a del(lp32) further implies that the TCL5 gene may play a role in malignant transformation.

p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

“…The TAL1 (or SCL) gene was originally identi®ed from its involvement by a recurrent chromosomal translocation in patients with T-cell acute lymphoblastic leukemia (T-ALL) (Begley et al, 1989a;Chen et al, 1990;Finger et al, 1989). Interstitial deletions that fuse TAL1 coding sequences to the promoter of an upstream gene, SIL (for SCL interrupting locus), were found subsequently to occur with greater frequency than translocations (Aplan et al, 1990;Bernard et al, 1990;Brown et al, 1990).…”

The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice

“…The SCL (TAL-1/TCL5) gene was ®rst identi®ed by its involvement in a t(1;14)(p32;q11) chromosomal translocation seen in 3% of childhood T-cell acute lymphoblastic leukemia (T-ALL) (Begley et al, 1989;Finger et al, 1989;Chen et al, 1990). Scl is a member of the basic helix ± loop ± helix (bHLH) family of transcription factors.…”

Frequent clonal loss of heterozygosity (LOH) in the chromosomal region 1p32 occurs in childhood T cell acute lymphoblastic leukemia (T-ALL) carrying rearrangements of the TAL1 gene

“…1 One of the most common genetic changes is the breakHigh molecular weight DNA was extracted according to stanage of the TAL1 gene. [3][4][5][6][7][8][9][10][11][12][13] As a consequence of the translodard procedures. 16 Ten micrograms of DNA were digested cation, the TAL1 gene, originally described to be involved in with HindIII, size-fractionated on 0.7% agarose gels and transthe t(1;14)(p32;q11) translocation, is juxtaposed with ferred to nylon membranes (Gene Screen Plus; Biotechnology sequences from the TCR ␣/␦ chain locus.…”

“…16 Ten micrograms of DNA were digested cation, the TAL1 gene, originally described to be involved in with HindIII, size-fractionated on 0.7% agarose gels and transthe t(1;14)(p32;q11) translocation, is juxtaposed with ferred to nylon membranes (Gene Screen Plus; Biotechnology sequences from the TCR ␣/␦ chain locus. [3][4][5][6][7][8] Although this System New Research Products, Boston, MA, USA) as translocation occurs in less than 3% of T-ALL patients, 8 sitedescribed. 14 TAL1 deletion was studied using a 32 P randomspecific deletions in the TAL1 gene are reported to occur in labelled SILDB probe.…”

“…Although the number of patients limited any definitive conclusions on the rate of frequency of LOH in childhood T-ALL, our findings indicate that LOH occurs in a region 1p32 known to be involved in translocations and site-specific deletions. [3][4][5][6][7][8][9][10][11][12][13] The two most useful markers in identifying LOH have been D1S200 and D1S211 suggesting the existence of hot spot regions of deletion.…”