Regulation of a novel target gene, aldehyde dehydrogenase 1, by HOX11 in childhood leukaemia

Funded Activity Summary

Leukaemia is the most common cancer of childhood. Patients with the T-cell form of this disease (T-ALL), often carry specific chromosomal abnormalities that result in the activation of genes specifying transcription factors (TF's). TF's determine which genes are expressed in any given cell type, but when present in the wrong cell type at the wrong time may initiate cancer due to the combined activity of target genes under their control. The identification of target genes involved in cancer is therefore essential in order to understand the mechanisms by which TF oncogenes induce tumour growth. However, very few target genes of TF's implicated in T-ALL have been discovered. HOX11 is one example of a TF aberrently expressed in childhood T-ALL. Recently we have shown that a gene called ALDH1 is under the control of HOX11 in a model cell system and also during normal development. The proper control of ALDH1 expression is important to the cell because it functions in the conversion of vitamin A to retinoic acid, a signalling molecule that critically affects cell growth and development. A related gene called RALDH2, that is also involved in retinoic acid synthesis, has very recently been shown to be under the control of other TF's implicated in T-ALL. These two discoveries therefore suggest that this disease may occur via a common pathway involving altered retinoic acid signalling. This project seeks to find out whether ALDH1 is also a target of HOX11 in T-ALL and if so, what effects it has on the cell. It also aims to determine how HOX11 influences the expression of ALDH1 and whether there are any other genes controlled by HOX11 that may be involved in tumour development. HOX11 provides an ideal model system to study the events leading to cancer that occur as a result of abnormal control of gene expression. Ultimately, such studies may lead to a better understanding of our normal biology as well as provide the basis for the design of improved cancer therapies.

Funded Activity Details

Start Date: 01-01-2000

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $382,027.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Biochemistry And Cell Biology Not Elsewhere Classified

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Cancer | Childhood leukaemia | HOX11 target gene | Haematology | Oncogene | T-cell | Transcription factor

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