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Chromosomal rearrangements involving band 12p13 are found in a wide variety of human leukemias but are particularly common in childhood acute lymphoblastic leukemia. The genes involved in these rearrangements, however, have not been identified. We now report the cloning of a t(12;21) translocation breakpoint involving 12p13 and 21q22 in two cases of childhood pre-B acute lymphoblastic leukemia, in which t(12;21) rearrangements were not initially apparent. The consequence of the translocation is fusion of the helix-loop-helix domain of TEL, an ETS-like putative transcription factor, to the DNA-binding and transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet-derived growth factor receptor beta in chronic myelomonocytic leukemia, can be implicated in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase or a transcription factor. The TEL-AML1 fusion also indicates that translocations affecting the AML1 gene can be associated with lymphoid, as well as myeloid, malignancy.

Titel:	Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.
Autor/in / Beteiligte Person:	Golub, TR ; Barker, GF ; Bohlander, SK ; Hiebert, SW ; Ward, DC ; Bray-Ward, P ; Morgan, E ; Raimondi, SC ; Rowley, JD ; Gilliland, DG
Link:	Zum Volltext
Zeitschrift:	Proceedings of the National Academy of Sciences of the United States of America, Jg. 92 (1995-05-23), Heft 11, S. 4917
Veröffentlichung:	Washington, DC : National Academy of Sciences, 1995
Medientyp:	academicJournal
ISSN:	0027-8424 (print)
DOI:	10.1073/pnas.92.11.4917
Schlagwort:	Amino Acid Sequence Base Sequence Blotting, Southern Bone Marrow pathology Child, Preschool Chromosome Mapping Core Binding Factor Alpha 2 Subunit DNA Primers Helix-Loop-Helix Motifs Humans Karyotyping Molecular Sequence Data Polymerase Chain Reaction Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology Proto-Oncogene Proteins c-ets ETS Translocation Variant 6 Protein Chromosomes, Human, Pair 12 Chromosomes, Human, Pair 21 Cloning, Molecular DNA-Binding Proteins genetics Gene Rearrangement Neoplasm Proteins genetics Oncogene Proteins, Fusion Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics Proto-Oncogene Proteins Repressor Proteins Transcription Factors genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. Language: English [Proc Natl Acad Sci U S A] 1995 May 23; Vol. 92 (11), pp. 4917-21. MeSH Terms: Chromosomes, Human, Pair 12* ; Chromosomes, Human, Pair 21* ; Cloning, Molecular* ; Gene Rearrangement* ; Oncogene Proteins, Fusion* ; Proto-Oncogene Proteins* ; Repressor Proteins* ; DNA-Binding Proteins / genetics ; Neoplasm Proteins / genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics ; Transcription Factors / genetics ; Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; Bone Marrow / pathology ; Child, Preschool ; Chromosome Mapping ; Core Binding Factor Alpha 2 Subunit ; DNA Primers ; Helix-Loop-Helix Motifs ; Humans ; Karyotyping ; Molecular Sequence Data ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology ; Proto-Oncogene Proteins c-ets ; ETS Translocation Variant 6 Protein References: Anal Biochem. 1989 Mar;177(2):282-6. (PMID: 2729546) ; Genes Chromosomes Cancer. 1995 Jan;12(1):66-9. (PMID: 7534114) ; Blood. 1992 Oct 1;80(7):1825-31. (PMID: 1391946) ; Cancer Genet Cytogenet. 1992 Oct 15;63(2):81-8. (PMID: 1423235) ; Eur J Biochem. 1993 Jan 15;211(1-2):7-18. (PMID: 8425553) ; Blood. 1993 May 1;81(9):2237-51. (PMID: 8481506) ; Methods Enzymol. 1993;218:340-56. (PMID: 7685466) ; Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6859-63. (PMID: 8341710) ; Science. 1993 Aug 20;261(5124):1041-4. (PMID: 8351518) ; Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7784-8. (PMID: 8395054) ; EMBO J. 1994 Feb 1;13(3):504-10. (PMID: 8313895) ; Genes Chromosomes Cancer. 1993 Dec;8(4):205-18. (PMID: 7512363) ; Cell. 1994 Apr 22;77(2):307-16. (PMID: 8168137) ; Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4004-8. (PMID: 8171026) ; Genes Chromosomes Cancer. 1994 Mar;9(3):186-91. (PMID: 7515661) ; Blood. 1994 Nov 15;84(10):3473-82. (PMID: 7949101) ; Genomics. 1994 Sep 15;23(2):425-32. (PMID: 7835892) ; Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10431-4. (PMID: 1720541) Grant Information: CA 20180 United States CA NCI NIH HHS; CA 21765 United States CA NCI NIH HHS; R01-CA 64140 United States CA NCI NIH HHS Gene Symbol: AML1; TEL Molecular Sequence: GENBANK S78496 Substance Nomenclature: 0 (Core Binding Factor Alpha 2 Subunit) ; 0 (DNA Primers) ; 0 (DNA-Binding Proteins) ; 0 (Neoplasm Proteins) ; 0 (Oncogene Proteins, Fusion) ; 0 (Proto-Oncogene Proteins) ; 0 (Proto-Oncogene Proteins c-ets) ; 0 (RUNX1 protein, human) ; 0 (Repressor Proteins) ; 0 (TEL-AML1 fusion protein) ; 0 (Transcription Factors) Entry Date(s): Date Created: 19950523 Date Completed: 19950629 Latest Revision: 20231213 Update Code: 20240513 PubMed Central ID: PMC41818

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Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.