Aberrant expression of aldehyde dehydrogenase 1A (ALDH1A) subfamily genes in acute lymphoblastic leukaemia is a common feature of T‐lineage tumours. (11th September 2014)

• Record Type: Journal Article
• Authors: Longville, Brooke A. C.; Anderson, Denise; Welch, Mathew D.; Kees, Ursula R.; Greene, Wayne K.
• Is Part Of: British journal of haematology. Volume 168:Number 2(2015:Jan.)
• Page Start: 246
• Page End: 257
• Publication Date: 2014-09-11
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13120
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13120-abs-0001"> <title>Summary</title> <p>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 <italic>ALDH1A</italic> genes, particularly <italic>ALDH1A2</italic>, in a majority (72%) of primary paediatric T cell acute lymphoblastic leukaemia (T‐ALL) specimens. <italic>ALDH1A</italic> 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 <italic>ALDH1A2</italic> 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 <italic>TNFRSF10B</italic> gene<italic>, </italic> encoding the apoptotic death receptor TNFRSF10B (also termed TRAIL‐R2), which negatively correlated with <italic>ALDH1A2</italic> 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.</p> </abstract>