Journal article
Aberrant expression of aldehyde dehydrogenase 1A (ALDH1A) subfamily genes in acute lymphoblastic leukaemia is a common feature of T-lineage tumours
British Journal of Haematology, Vol.168(2), pp.246-257
2014
Abstract
The class 1A aldehyde dehydrogenase (ALDH1A) subfamily of genes encode enzymes that function at the apex of the retinoic acid (RA) signalling pathway. We detected aberrant expression of ALDH1A genes, particularly ALDH1A2, in a majority (72%) of primary paediatric T cell acute lymphoblastic leukaemia (T-ALL) specimens. ALDH1A expression was almost exclusive to T-lineage, but not B-lineage, ALL. To determine whether ALDH1A expression may have relevance to T-ALL cell growth and survival, the effect of inhibiting ALDH1A function was measured on a panel of human ALL cell lines. This revealed that T-ALL proliferation had a higher sensitivity to modulation of ALDH1A activity and RA signalling as compared to ALL cell lines of B-lineage. Consistent with these findings, the genes most highly correlated with ALDH1A2 expression were involved in cell proliferation and apoptosis. Evidence that such genes may be targets of regulation via RA signalling initiated by ALDH1A activity was provided by the TNFRSF10B gene, encoding the apoptotic death receptor TNFRSF10B (also termed TRAIL-R2), which negatively correlated with ALDH1A2 and showed elevated transcription following treatment of T-ALL cell lines with the ALDH1A inhibitor citral (3,7-dimethyl-2,6-octadienal). These data indicate that ALDH1A expression is a common event in T-ALL and supports a role for these enzymes in the pathobiology of this disease.
Details
- Title
- Aberrant expression of aldehyde dehydrogenase 1A (ALDH1A) subfamily genes in acute lymphoblastic leukaemia is a common feature of T-lineage tumours
- Authors/Creators
- B.A.C. Longville (Author/Creator) - The Kids Research Institute AustraliaD. Anderson (Author/Creator) - The Kids Research Institute AustraliaM.D. Welch (Author/Creator) - ARC Centre of Excellence in Plant Energy BiologyU.R. Kees (Author/Creator) - The Kids Research Institute AustraliaW.K. Greene (Author/Creator) - Murdoch University
- Publication Details
- British Journal of Haematology, Vol.168(2), pp.246-257
- Publisher
- Blackwell Publishing Inc.
- Identifiers
- 991005542922307891
- Copyright
- © 2014 John Wiley & Sons Ltd
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Web Of Science research areas
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