期刊
BLOOD
卷 123, 期 7, 页码 1021-1031出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2013-04-490847
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资金
- European Research Council [250333]
- Sidaction (Fonds de dotation PIERRE BERGE)
- Agence Nationale de Recherche sur le Sida
- European FP7 HIT HIDDEN HIV [305762]
- Ministere de l'Enseignement surperieur et de la Recherche fellowships
- Oxford Partnership Comprehensive Biomedical Research Centre
- Department of Health's National Institute for Health Research Biomedical Research Centres
- Health Innovation Challenge Fund [HICF-1009-026]
- Wellcome Trust
- Department of Health
- Wellcome Trust Core Award Grant [090532/Z/09/Z]
- European Union's Seventh Framework Programme (FP7) [241779]
- Wellcome Trust [090532/Z/09/Z] Funding Source: Wellcome Trust
- MRC [MC_UU_12010/8] Funding Source: UKRI
- Medical Research Council [MC_UU_12010/8] Funding Source: researchfish
- National Institute for Health Research [07/01/38] Funding Source: researchfish
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-Goutieres 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.
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