Advertisement

The TEL Gene Contributes to the Pathogenesis of Myeloid and Lymphoid Leukemias by Diverse Molecular Genetic Mechanisms

  • T. R. Golub
  • G. F. Barker
  • K. Stegmaier
  • D. G. Gilliland
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 220)

Abstract

The TEL gene, originally cloned by virtue of involvement in the t(5;12) chromosomal translocation associated with chronic myelomonocytic leukemia (CMML), has a remarkable capacity to contribute to the pathogenesis of human leukemias: (1) TEL has been implicated in both myeloid and lymphoid leukemias, acute and chronic leukemias, and leukemias of both pediatric and adult populations; (2) TEL can contribute either its DNA binding domain or a putative helix-loop-helix (HLH) domain to fusion proteins, and (3) TEL has been associated with a surprising variety of fusion partners in human leukemias, including genes for transcription factors, receptor and non-receptor tyrosine kinases, and putative transcriptional activating domains. In addition, recent evidence suggests that loss of function of TEL may also contribute to pathogenesis of malignancy. In this report, the diverse molecular genetic mechanisms of leukemogenesis mediated by the TEL gene will be discussed.

Keywords

Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Fusion Partner Tyrosine Kinase Domain Lymphoid Leukemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, van Kessel AG, Riegman P, Deprez RL, Zwartoff E, Hagemeijer A, Grosveld G (1995) Translocation (12;22)(p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11. Oncogene 10: 1511 – 1519PubMedGoogle Scholar
  2. Golub TR, Barker GF, Lovett M, Gilliland DG (1994) Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77: 307 – 316PubMedCrossRefGoogle Scholar
  3. Golub T, Barker GF, Bohlander S, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD, Gilliland DG (1995a) Fusion of the TEL gene on 12p13 to the AML1 gene on 12q22 in acute lymphoblastic leukemia. Proc Natl Acad Sci 92: 4917 – 4921CrossRefGoogle Scholar
  4. Golub T, McLean T, Stegmaier K, Ritz J, Sallan S, Neuberg D, Gilliland DG (1995b) TEL-AML1: The most common gene rearrangement in childhood ALL. Blood (Suppl)Google Scholar
  5. Golub TR, Goga A, Barker GF, Afar D, McLaughlin J, Bohlander SK, Rowley JD, Witte ON, Gilliland DG (1996) Oligomerization of the ABL tyrosine kinase by the ETS protein TEL in human leukemia. Mol Cell Biol (in press)Google Scholar
  6. Nucifora G, Begy CR, Erickson P, Drabkin HA, Rowley JD (1993) The 3;21 translocation in myelo-dysplasia results in a fusion transcript between the AML1 gene and the gene for EAO, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc Natl Acad Sci USA 90: 7784 – 7788PubMedCrossRefGoogle Scholar
  7. Papadopoulos P, Ridge SA, Boucher CA, Stocking C, Wiedemann LM (1995) The novel activation of ABL by fusion to an ets-related gene, TEL. Cancer Res 55: 34 – 38PubMedGoogle Scholar
  8. Pendergast AM, Quilliam LA, Cripe LD, Bessing CH, Dai Z, Li N, Der CJ, Sclessinger J, Gishizky ML (1993) BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adapter protein Cell 75: 175 – 185Google Scholar
  9. Pui CH, Raimondi SC, Crist WM (1992) Chromosomal abnormalities in childhood acute lymphoblastic leukaemia. Recent Adv Haematol 6: 89 – 105Google Scholar
  10. Raimondi SC, Williams DL, Callihan T, Peiper S, Rivera GK, Murphy SB (1986) Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia. Blood 68: 69 – 75PubMedGoogle Scholar
  11. Romana SP, Mauchauffe M, LeConiat M, LePaslier D, Berger R, Bernard OA (1995) The t(12;21) of acute lymphoblastic leukemia results in a TEL-AML1 gene fusion. Blood 85: 3662 – 3670PubMedGoogle Scholar
  12. Sato Y, Suto Y, Pietenpol J, Golub TR, Gilliland DG, Davis EM, LeBeau MM, Roberts J, Vogelstein B, Rowley JD, Bohlander SK (1995) TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoeitic malignancies. Blood 86: 1525 – 1533PubMedGoogle Scholar
  13. Shimizu K, Ichikawa H, Tojo A, Kaneko Y, Maseki N, Hayashi Y, Ohira M, Asano S, Ohki M (1993) An ets-related gene, ERG, is rearranged in human myeloid leukemia with t(16;21) chromosomal translocation. Proc Natl Acad Sci USA 90: 10280 – 10284PubMedCrossRefGoogle Scholar
  14. Sorensen PHB, Lessnick AL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT (1994) A second Ewing’s sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nature Genetics 6: 146 – 151PubMedCrossRefGoogle Scholar
  15. Stegmaier K, Pendse S, Barker GF, Bray-Ward P, Ward DC, Montgomery KT, Krauter K, Reynolds C, Sklar J, Donnelly M, Bohlander SK, Rowley JD, Sallan SE, Gilliland DG, Golub TR (1995) Frequent loos of heterzygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood. Blood 86: 38 – 44PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • T. R. Golub
    • 1
  • G. F. Barker
    • 1
  • K. Stegmaier
    • 1
  • D. G. Gilliland
    • 1
  1. 1.Howard Hughes Medical Institute and the Division of Hematology/Oncology, Department of Medicine, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA

Personalised recommendations