Search: onr:"swepub:oai:lup.lub.lu.se:e77f9af1-641c-4369-9c48-bb4dad0ae268" >
Genetic and regulat...
Genetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10p21.2
-
- Studd, James B. (author)
- Institute of Cancer Research London
-
- Vijayakrishnan, Jayaram (author)
- Institute of Cancer Research London
-
- Yang, Minjun (author)
- Lund University,Lunds universitet,Aneuploidi i cancer,Forskargrupper vid Lunds universitet,Aneuploidy in cancer,Lund University Research Groups
-
show more...
-
- Migliorini, Gabriele (author)
- Institute of Cancer Research London
-
- Paulsson, Kajsa (author)
- Lund University,Lunds universitet,Aneuploidi i cancer,Forskargrupper vid Lunds universitet,Aneuploidy in cancer,Lund University Research Groups
-
- Houlston, Richard S. (author)
- Institute of Cancer Research London
-
show less...
-
(creator_code:org_t)
- 2017-03-03
- 2017
- English.
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
- Related links:
-
http://dx.doi.org/10... (free)
-
show more...
-
https://doi.org/10.1...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Despite high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL) being the most common subgroup of paediatric ALL, its aetiology remains unknown. Genome-wide association studies have demonstrated association at 10q21.2. Here, we sought to determine how this region influences HD-ALL risk. We impute genotypes across the locus, finding the single nucleotide polymorphism rs7090445 highly associated with HD-ALL (P=1.54 × 10'38), and residing in a predicted enhancer element. We show this region physically interacts with the transcription start site of ARID5B, that alleles of rs7090445 have differential enhancer activity and influence RUNX3 binding. RUNX3 knock-down reduces ARID5B expression and rs7090445 enhancer activity. Individuals carrying the rs7090445-C risk allele also have reduced ARID5B expression. Finally, the rs7090445-C risk allele is preferentially retained in HD-ALL blasts consistent with inherited genetic variation contributing to arrest of normal lymphocyte development, facilitating leukaemic clonal expansion. These data provide evidence for a biological mechanism underlying hereditary risk of HD-ALL at 10q21.2.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database