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Aberrant expression of aldehyde dehydrogenase 1A ( ALDH 1A) subfamily genes in acute lymphoblastic leukaemia is a common feature of T‐lineage tumours
Author(s) -
Longville Brooke A. C.,
Anderson Denise,
Welch Mathew D.,
Kees Ursula R.,
Greene Wayne K.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13120
Subject(s) - aldehyde dehydrogenase , biology , gene , aldh2 , transcription factor , cancer research , programmed cell death , apoptosis , microbiology and biotechnology , genetics
Summary The class 1A aldehyde dehydrogenase ( ALDH 1A) subfamily of genes encode enzymes that function at the apex of the retinoic acid ( RA ) signalling pathway. We detected aberrant expression of ALDH 1A genes, particularly ALDH 1A2 , in a majority (72%) of primary paediatric T cell acute lymphoblastic leukaemia (T‐ ALL ) specimens. ALDH 1A expression was almost exclusive to T‐lineage, but not B‐lineage, ALL . To determine whether ALDH 1A expression may have relevance to T‐ ALL cell growth and survival, the effect of inhibiting ALDH 1A function was measured on a panel of human ALL cell lines. This revealed that T‐ ALL proliferation had a higher sensitivity to modulation of ALDH 1A activity and RA signalling as compared to ALL cell lines of B‐lineage. Consistent with these findings, the genes most highly correlated with ALDH 1A2 expression were involved in cell proliferation and apoptosis. Evidence that such genes may be targets of regulation via RA signalling initiated by ALDH 1A activity was provided by the TNFRSF 10B gene , encoding the apoptotic death receptor TNFRSF 10B (also termed TRAIL ‐R2), which negatively correlated with ALDH 1A2 and showed elevated transcription following treatment of T‐ ALL cell lines with the ALDH 1A inhibitor citral (3,7‐dimethyl‐2,6‐octadienal). These data indicate that ALDH 1A expression is a common event in T‐ ALL and supports a role for these enzymes in the pathobiology of this disease.