Home LiteratureArticle Details
PMID: 2501659 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein.

Molecular and cellular biology ·Vol. 9 ·No. 5 ·1989-05-00 ·Pages 2124-32

McGuire EA, Hockett RD, Pollock KM, Bartholdi MF, O'Brien SJ, Korsmeyer SJ

Abstract

Interchromosomal translocations within lymphoid neoplasms frequently involve the antigen receptor genes. We cloned the breakpoints of the t(11;14)(p15;q11) in a CD3-negative T-cell acute lymphoblastic leukemia cell line (RPMI 8402) in order to identify new genes potentially involved in T-cell neoplasia. An extensive comparison of both breakpoints and their germ line counterparts indicated that an inadvertant recombinase-mediated break at chromosome segment 11p15 recombined with the delta T-cell receptor at 14q11. The derivative 11 breakpoint resembles a coding joint in which 11p15 rather than a variable region was introduced 5' to a D delta 1 D delta 2 J delta 1 intermediate rearrangement. Conversely, the derivative 14 breakpoint corresponds to a signal joint between the 5' heptamer-spacer-nonamer recombinational signal of D delta 1 and an isolated heptamer at 11p15. Multiple, apparently distinct transcripts were found flanking both breakpoints of 8402. RNAs of 3.5, 4.4, 1.4, and 8.0 kilobases originating from either side of the derivative 14 breakpoint were highly expressed in 8402 compared with other cells. This suggests that this translocation deregulated multiple genes and provides the opportunity to assess any multifactorial contribution they may have to malignancy. We cloned and sequenced several cDNAs representing the 1.4-kilobase transcript (termed Ttg-1 [T-cell translocation gene 1]) from an 8402 library. The predicted protein of 156 amino acids contained two internal repeats which could potentially form zinc fingers.

MeSH Terms
Amino Acid Sequence Base Sequence Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 14 DNA/genetics DNA-Binding Proteins/genetics Humans Leukemia-Lymphoma, Adult T-Cell/genetics Metalloproteins/genetics Molecular Sequence Data Restriction Mapping Transcription, Genetic Translocation, Genetic
Chemicals
DNA-Binding Proteins Metalloproteins DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
McGuire E A
Department of Medicine, Howard Hughes Medical Institute, Washington University, St. Louis, Missouri 63110.
Hockett R D
Pollock K M
Bartholdi M F
O'Brien S J
Korsmeyer S J
References (54)
54 references, click to expand
  1. Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias.
    Science. 1985 Aug 23;229(4715):784-6 PMID: 3875152
  2. Extensive junctional diversity of rearranged human T cell receptor delta genes.
    Science. 1988 Jun 10;240(4858):1541-4 PMID: 3259726
  3. Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product.
    Nature. 1988 Jul 14;334(6178):124-9 PMID: 2968522
  4. Zinc fingers: a novel protein fold for nucleic acid recognition.
    Cold Spring Harb Symp Quant Biol. 1987;52:473-82 PMID: 3135979
  5. Metal ions in proteins: structural and functional roles.
    Cold Spring Harb Symp Quant Biol. 1987;52:579-85 PMID: 3454279
  6. Immunoglobulin and T-cell receptor genes reveal the clonality, lineage, and translocations of lymphoid neoplasms.
    Important Adv Oncol. 1987;:3-25 PMID: 3136076
  7. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments.
    EMBO J. 1988 Jun;7(6):1661-8 PMID: 2971534
  8. Genomic organization of the human T-cell antigen-receptor alpha/delta locus.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):8166-70 PMID: 3186718
  9. Human T-cell antigen receptor (TCR) delta-chain locus and elements responsible for its deletion are within the TCR alpha-chain locus.
    Proc Natl Acad Sci U S A. 1988 Dec;85(24):9694-8 PMID: 2974161
  10. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.
    Cell. 1986 Jan 31;44(2):283-92 PMID: 3943125
  11. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators.
    Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670-4 PMID: 2419912
  12. Developmental regulation of a gene that encodes a cysteine-rich intestinal protein and maps near the murine immunoglobulin heavy chain locus.
    Proc Natl Acad Sci U S A. 1986 Apr;83(8):2516-20 PMID: 3085096
  13. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition.
    Annu Rev Immunol. 1986;4:529-91 PMID: 3518750
  14. Rearrangement and expression of the alpha, beta, and gamma chain T cell receptor genes in human thymic leukemia cells and functional T cells.
    J Exp Med. 1986 Jun 1;163(6):1491-508 PMID: 3486937
  15. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene.
    Science. 1986 Jul 11;233(4760):212-4 PMID: 3460176
  16. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation.
    Cell. 1986 Aug 29;46(5):659-67 PMID: 3488815
  17. Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development.
    Science. 1986 Oct 10;234(4773):197-200 PMID: 3092355
  18. An adenovirus E1a protein region required for transformation and transcriptional repression.
    Cell. 1986 Sep 26;46(7):1043-51 PMID: 2944600
  19. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation.
    Cell. 1986 Oct 10;47(1):19-28 PMID: 2875799
  20. The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript.
    Mol Cell Biol. 1986 Feb;6(2):607-16 PMID: 3023859
  21. Adenovirus promoters and E1A transactivation.
    Annu Rev Genet. 1986;20:45-79 PMID: 3028247
  22. T cell receptor beta gene sequences in the circular DNA of thymocyte nuclei: direct evidence for intramolecular DNA deletion in V-D-J joining.
    Cell. 1987 May 22;49(4):477-85 PMID: 3502705
  23. Isolation of an excision product of T-cell receptor alpha-chain gene rearrangements.
    Nature. 1987 May 21-27;327(6119):242-3 PMID: 3033520
  24. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation.
    Nature. 1987 Jun 25-Jul 1;327(6124):677-82 PMID: 2439914
  25. T cell receptor alpha-, beta-, and gamma-genes in T cell and pre-B cell acute lymphoblastic leukemia.
    J Clin Invest. 1987 Aug;80(2):545-56 PMID: 3497178
  26. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity.
    Nature. 1987 Oct 15-21;329(6140):642-5 PMID: 3657987
  27. Deletional rearrangement in the human T-cell receptor alpha-chain locus.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8608-12 PMID: 3500476
  28. Mutations in the first exon are associated with altered transcription of c-myc in Burkitt lymphoma.
    Science. 1987 Nov 27;238(4831):1272-5 PMID: 3685977
  29. Chromosome sorting by flow cytometry.
    Methods Enzymol. 1987;151:252-67 PMID: 3431443
  30. Chromosomal translocation involving the beta T cell receptor gene in acute leukemia.
    J Exp Med. 1988 Feb 1;167(2):682-7 PMID: 3162254
  31. Sequence and organization of the human T cell delta chain gene.
    Eur J Immunol. 1988 Feb;18(2):283-7 PMID: 2965024
  32. Alternative promoters and exons, somatic mutation and deregulation of the Bcl-2-Ig fusion gene in lymphoma.
    EMBO J. 1988 Jan;7(1):123-31 PMID: 2834197
  33. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15.
    EMBO J. 1988 Feb;7(2):385-94 PMID: 3259177
  34. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining.
    Nature. 1973 Jun 1;243(5405):290-3 PMID: 4126434
  35. Cytogenetic study of human lymphoid T-cell lines derived from lymphocytic leukemia.
    J Natl Cancer Inst. 1974 Sep;53(3):655-60 PMID: 4547172
  36. Establishment and characterization of a human histiocytic lymphoma cell line (U-937).
    Int J Cancer. 1976 May 15;17(5):565-77 PMID: 178611
  37. A specific transcription factor that can bind either the 5S RNA gene or 5S RNA.
    Proc Natl Acad Sci U S A. 1980 Jul;77(7):4170-4 PMID: 7001457
  38. The role of gene dosage and genetic transpositions in carcinogenesis.
    Nature. 1981 Nov 26;294(5839):313-8 PMID: 7312030
  39. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma.
    N Engl J Med. 1982 Nov 11;307(20):1231-6 PMID: 7133054
  40. Rapid similarity searches of nucleic acid and protein data banks.
    Proc Natl Acad Sci U S A. 1983 Feb;80(3):726-30 PMID: 6572363
  41. Somatic generation of antibody diversity.
    Nature. 1983 Apr 14;302(5909):575-81 PMID: 6300689
  42. Dispersion of the ras family of transforming genes to four different chromosomes in man.
    Nature. 1983 Apr 28;302(5911):839-42 PMID: 6843651
  43. Mapping of an endogenous retroviral sequence to human chromosome 18.
    Nature. 1983 May 5-11;303(5912):74-7 PMID: 6843662
  44. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
    Anal Biochem. 1983 Jul 1;132(1):6-13 PMID: 6312838
  45. New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia.
    Cell. 1984 Jan;36(1):101-9 PMID: 6607116
  46. Novel kappa light-chain gene rearrangements in mouse lambda light chain-producing B lymphocytes.
    Nature. 1984 Feb 23-29;307(5953):749-52 PMID: 6422305
  47. Localization of a T-cell receptor diversity-region element.
    Nature. 1984 Aug 2-8;310(5976):421-3 PMID: 6611508
  48. The structure, rearrangement and expression of D beta gene segments of the murine T-cell antigen receptor.
    Nature. 1984 Sep 27-Oct 3;311(5984):344-50 PMID: 6090932
  49. Rapid and sensitive protein similarity searches.
    Science. 1985 Mar 22;227(4693):1435-41 PMID: 2983426
  50. Transcription termination and 3' processing: the end is in site!
    Cell. 1985 Jun;41(2):349-59 PMID: 2580642
  51. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia.
    Nature. 1985 Jun 13-19;315(6020):550-4 PMID: 2989692
  52. A uniform deleting element mediates the loss of kappa genes in human B cells.
    Nature. 1985 Jul 18-24;316(6025):260-2 PMID: 3927169
  53. Cloning of the gene encoding the delta subunit of the human T-cell receptor reveals its physical organization within the alpha-subunit locus and its involvement in chromosome translocations in T-cell malignancy.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):3933-7 PMID: 2836865
  54. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice.
    Nature. 1985 Dec 12-18;318(6046):533-8 PMID: 3906410
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1989-05-00
Pages
2124-32
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363006
Subset
IM
Grants
NCRR NIH HHS · RR01315 · United States
Databases
GENBANK
M26680, M26681, M26682
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]