Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia
Authors:
- 24 May 2004
- journal article
- review article
- Published by Springer Nature in Oncogene
- Vol. 23 (24) , 4275-4283
Abstract
Balanced chromosomal translocations are frequently associated with haematopoietic neoplasms and often involve genes that encode transcription factors, which play critical roles in normal haematopoiesis. Fusion oncoproteins that arise from chimeric genes generated by such translocations are usually stable and consistent molecular markers for a given disease subtype and contribute to the leukaemogenic processes. The t(12;21)(p13;q22) chromosomal translocation is the most frequent illegitimate gene recombination in paediatric cancer, occurring in approximately 25% of common (c) B-cell precursor acute lymphoblastic leukaemia (cALL) cases. The rearrangement results in the in-frame fusion of the 5' region of the ETS-related gene, TEL (ETV6), to almost the entire AML1 (RUNX1) locus and is associated with favourable prognosis following conventional therapeutic strategies. We discuss here the prenatal origins of the TEL/AML1 translocation as an initiating mutation, the role of TEL-AML1 in cellular transformation and the molecular mechanisms by which the chimeric protein imposes altered patterns of gene expression.Keywords
This publication has 103 references indexed in Scilit:
- Protracted postnatal natural histories in childhood leukemiaGenes, Chromosomes and Cancer, 2004
- Origins of chromosome translocations in childhood leukaemiaNature Reviews Cancer, 2003
- Low NAD(P)H:quinone oxidoreductase activity is associated with increased risk of leukemia with MLL translocations in infants and childrenBlood, 2002
- In vivo analysis of the molecular pathogenesis of acute promyelocytic leukemia in the mouse and its therapeutic implicationsOncogene, 1999
- Molecular genetics, natural history and the demise of childhood leukaemiaEuropean Journal of Cancer, 1999
- TLE, the Human Homolog of Groucho, Interacts with AML1 and Acts as a Repressor of AML1-Induced TransactivationBiochemical and Biophysical Research Communications, 1998
- Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cellNature Medicine, 1997
- The multistep nature of cancerTrends in Genetics, 1993
- Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cellsCancer Genetics and Cytogenetics, 1992
- Dangerous ConnectionsPhysiotherapy, 1988