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

Todd R. Golub, George F. Barker, Stefan K. Bohlander, Scott W. Hiebert, David C. Ward, Patricia Bray-Ward, Elaine R Morgan, Susana C. Raimondi, Janet D. Rowley, D. Gary Gilliland*

*Corresponding author for this work

Research output: Contribution to journalArticle

641 Citations (Scopus)

Abstract

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 anti transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet- derived growth factor receptor β 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.

Original languageEnglish (US)
Pages (from-to)4917-4921
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number11
DOIs
StatePublished - May 23 1995

Fingerprint

Gene Fusion
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Transcription Factors
Leukemia
Helix-Loop-Helix Motifs
Leukemia, Myelomonocytic, Chronic
Genes
Platelet-Derived Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Transcriptional Activation
Organism Cloning
DNA
Neoplasms

Keywords

  • ETS
  • chromosome 12
  • chromosome 21
  • transcription factors
  • translocation

ASJC Scopus subject areas

  • General

Cite this

Golub, T. R., Barker, G. F., Bohlander, S. K., Hiebert, S. W., Ward, D. C., Bray-Ward, P., ... Gilliland, D. G. (1995). Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proceedings of the National Academy of Sciences of the United States of America, 92(11), 4917-4921. https://doi.org/10.1073/pnas.92.11.4917
Golub, Todd R. ; Barker, George F. ; Bohlander, Stefan K. ; Hiebert, Scott W. ; Ward, David C. ; Bray-Ward, Patricia ; Morgan, Elaine R ; Raimondi, Susana C. ; Rowley, Janet D. ; Gilliland, D. Gary. / Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 11. pp. 4917-4921.
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abstract = "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 anti transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet- derived growth factor receptor β 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.",
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Golub, TR, Barker, GF, Bohlander, SK, Hiebert, SW, Ward, DC, Bray-Ward, P, Morgan, ER, Raimondi, SC, Rowley, JD & Gilliland, DG 1995, 'Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia', Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 11, pp. 4917-4921. https://doi.org/10.1073/pnas.92.11.4917

Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. / Golub, Todd R.; Barker, George F.; Bohlander, Stefan K.; Hiebert, Scott W.; Ward, David C.; Bray-Ward, Patricia; Morgan, Elaine R; Raimondi, Susana C.; Rowley, Janet D.; Gilliland, D. Gary.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 11, 23.05.1995, p. 4917-4921.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia

AU - Golub, Todd R.

AU - Barker, George F.

AU - Bohlander, Stefan K.

AU - Hiebert, Scott W.

AU - Ward, David C.

AU - Bray-Ward, Patricia

AU - Morgan, Elaine R

AU - Raimondi, Susana C.

AU - Rowley, Janet D.

AU - Gilliland, D. Gary

PY - 1995/5/23

Y1 - 1995/5/23

N2 - 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 anti transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet- derived growth factor receptor β 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.

AB - 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 anti transactivation domains of the transcription factor AML1. These data show that TEL, previously shown to be fused to the platelet- derived growth factor receptor β 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.

KW - ETS

KW - chromosome 12

KW - chromosome 21

KW - transcription factors

KW - translocation

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U2 - 10.1073/pnas.92.11.4917

DO - 10.1073/pnas.92.11.4917

M3 - Article

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SP - 4917

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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