SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage.
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 sequenci...
मुख्य लेखकों: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
स्वरूप: | Journal article |
भाषा: | English |
प्रकाशित: |
American Society of Hematology
2014
|
_version_ | 1826264025691848704 |
---|---|
author | Clifford, R Louis, T Robbe, P Ackroyd, S Burns, A Timbs, A Wright Colopy, G Dreau, H Sigaux, F Judde, J Rotger, M Telenti, A Lin, Y Pasero, P Maelfait, J Titsias, M Cohen, DR Henderson, S Ross, M Bentley, D Hillmen, P Pettitt, A Rehwinkel, J Knight, S Taylor, J |
author_facet | Clifford, R Louis, T Robbe, P Ackroyd, S Burns, A Timbs, A Wright Colopy, G Dreau, H Sigaux, F Judde, J Rotger, M Telenti, A Lin, Y Pasero, P Maelfait, J Titsias, M Cohen, DR Henderson, S Ross, M Bentley, D Hillmen, P Pettitt, A Rehwinkel, J Knight, S Taylor, J |
author_sort | Clifford, R |
collection | OXFORD |
description | 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. |
first_indexed | 2024-03-06T20:01:11Z |
format | Journal article |
id | oxford-uuid:2758a9e4-d71d-40cb-a73e-fab2144e552c |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T20:01:11Z |
publishDate | 2014 |
publisher | American Society of Hematology |
record_format | dspace |
spelling | oxford-uuid:2758a9e4-d71d-40cb-a73e-fab2144e552c2022-03-26T12:06:30ZSAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2758a9e4-d71d-40cb-a73e-fab2144e552cEnglishSymplectic Elements at OxfordAmerican Society of Hematology2014Clifford, RLouis, TRobbe, PAckroyd, SBurns, ATimbs, AWright Colopy, GDreau, HSigaux, FJudde, JRotger, MTelenti, ALin, YPasero, PMaelfait, JTitsias, MCohen, DRHenderson, SRoss, MBentley, DHillmen, PPettitt, ARehwinkel, JKnight, STaylor, JSAMHD1 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. |
spellingShingle | Clifford, R Louis, T Robbe, P Ackroyd, S Burns, A Timbs, A Wright Colopy, G Dreau, H Sigaux, F Judde, J Rotger, M Telenti, A Lin, Y Pasero, P Maelfait, J Titsias, M Cohen, DR Henderson, S Ross, M Bentley, D Hillmen, P Pettitt, A Rehwinkel, J Knight, S Taylor, J SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. |
title | SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. |
title_full | SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. |
title_fullStr | SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. |
title_full_unstemmed | SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. |
title_short | SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. |
title_sort | samhd1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to dna damage |
work_keys_str_mv | AT cliffordr samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT louist samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT robbep samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT ackroyds samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT burnsa samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT timbsa samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT wrightcolopyg samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT dreauh samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT sigauxf samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT juddej samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT rotgerm samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT telentia samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT liny samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT paserop samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT maelfaitj samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT titsiasm samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT cohendr samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT hendersons samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT rossm samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT bentleyd samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT hillmenp samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT pettitta samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT rehwinkelj samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT knights samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage AT taylorj samhd1ismutatedrecurrentlyinchroniclymphocyticleukemiaandisinvolvedinresponsetodnadamage |