The RAC specific guanine nucleotide exchange factor Asef functions downstream from TEL-AML1 to promote leukaemic transformation

Ruth Lyons; Owen Williams; Michelle Morrow; Neil Sebire; Mike Hubank; John Anderson

doi:10.1016/j.leukres.2009.06.032

The RAC specific guanine nucleotide exchange factor Asef functions downstream from TEL-AML1 to promote leukaemic transformation

Leuk Res. 2010 Jan;34(1):109-15. doi: 10.1016/j.leukres.2009.06.032. Epub 2009 Jul 22.

Authors

Ruth Lyons¹, Owen Williams, Michelle Morrow, Neil Sebire, Mike Hubank, John Anderson

Affiliation

¹ Unit of Molecular Haematology and Cancer Biology, University College London Institute of Child Health, London, United Kingdom.

PMID: 19628279
DOI: 10.1016/j.leukres.2009.06.032

Abstract

TEL-AML1 is an oncogenic fusion protein associated with childhood pre-B acute lymphoblastic leukaemia. From published microarray datasets we identified the Rho Guanine Nucleotide Exchange Factor (RhoGEF) Asef to be associated with TEL-AML1 leukaemia. However, the Asef gene is not a direct target of TEL-AML1 transcriptional control. Forced expression of Asef in vitro induced and maintained proliferation of haemaopoietic progenitor cells and co-operated with TEL-AML1 greatly to enhance proliferation and haemopoietic colony size. In haemopoietic transplantation reconstitution assays Asef and TEL-AML1 together failed to induce a leukaemic phenotype.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Cell Transformation, Neoplastic*
Core Binding Factor Alpha 2 Subunit / physiology*
Guanine Nucleotide Exchange Factors / physiology*
Hematopoietic Stem Cells / pathology
Humans
Leukemia / pathology*
Mice
Oncogene Proteins, Fusion / physiology*
Rho Guanine Nucleotide Exchange Factors

Substances

ARHGEF4 protein, human
Core Binding Factor Alpha 2 Subunit
Guanine Nucleotide Exchange Factors
Oncogene Proteins, Fusion
Rho Guanine Nucleotide Exchange Factors
TEL-AML1 fusion protein