SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage.

Details

Serval ID
serval:BIB_257E294D4C3F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage.
Journal
Blood
Author(s)
Clifford R., Louis T., Robbe P., Ackroyd S., Burns A., Timbs A.T., Wright Colopy G., Dreau H., Sigaux F., Judde J.G., Rotger M., Telenti A., Lin Y.L., Pasero P., Maelfait J., Titsias M., Cohen D.R., Henderson S.J., Ross M.T., Bentley D., Hillmen P., Pettitt A., Rehwinkel J., Knight S.J., Taylor J.C., Crow Y.J., Benkirane M., Schuh A.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
123
Number
7
Pages
1021-1031
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish PDF : Regular Article
Abstract
SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase and a nuclease that restricts HIV-1 in noncycling cells. Germ-line mutations in SAMHD1 have been described in patients with Aicardi-Goutières syndrome (AGS), a congenital autoimmune disease. In a previous longitudinal whole genome sequencing study of chronic lymphocytic leukemia (CLL), we revealed a SAMHD1 mutation as a potential founding event. Here, we describe an AGS patient carrying a pathogenic germ-line SAMHD1 mutation who developed CLL at 24 years of age. Using clinical trial samples, we show that acquired SAMHD1 mutations are associated with high variant allele frequency and reduced SAMHD1 expression and occur in 11% of relapsed/refractory CLL patients. We provide evidence that SAMHD1 regulates cell proliferation and survival and engages in specific protein interactions in response to DNA damage. We propose that SAMHD1 may have a function in DNA repair and that the presence of SAMHD1 mutations in CLL promotes leukemia development.
Keywords
Adult, Autoimmune Diseases of the Nervous System/complications, Autoimmune Diseases of the Nervous System/genetics, Cohort Studies, Comparative Genomic Hybridization, DNA Damage/genetics, Gene Frequency, Germ-Line Mutation, HeLa Cells, Humans, Leukemia, Lymphocytic, Chronic, B-Cell/complications, Leukemia, Lymphocytic, Chronic, B-Cell/genetics, Male, Monomeric GTP-Binding Proteins/genetics, Nervous System Malformations/complications, Nervous System Malformations/genetics, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2014 14:13
Last modification date
20/08/2019 13:04
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