The TEL Gene Contributes to the Pathogenesis of Myeloid and Lymphoid Leukemias by Diverse Molecular Genetic Mechanisms
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.
KeywordsAcute Myeloid Leukemia Acute Lymphoblastic Leukemia Fusion Partner Tyrosine Kinase Domain Lymphoid Leukemia
Unable to display preview. Download preview PDF.
- 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
- 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
- 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
- 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
- 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
- Pui CH, Raimondi SC, Crist WM (1992) Chromosomal abnormalities in childhood acute lymphoblastic leukaemia. Recent Adv Haematol 6: 89 – 105Google Scholar
- 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