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

Ruth Clifford; Tania Louis; Pauline Robbe; Sam Ackroyd; Adam Burns; Adele T. Timbs; Glen Wright Colopy; Helene Dreau; Francois Sigaux; Jean Gabriel Judde; Margalida Rotger; Amalio Telenti; Yea Lih Lin; Philippe Pasero; Jonathan Maelfait; Michalis Titsias; Dena R. Cohen; Shirley J. Henderson; Mark T. Ross; David Bentley; Peter Hillmen; Andrew Pettitt; Jan Rehwinkel; Samantha J.L. Knight; Jenny C. Taylor; Yanick J. Crow; Monsef Benkirane; Anna Schuh

doi:10.1182/blood-2013-04-490847

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

Ruth Clifford, Tania Louis, Pauline Robbe, Sam Ackroyd, Adam Burns, Adele T. Timbs, Glen Wright Colopy, Helene Dreau, Francois Sigaux, Jean Gabriel Judde, Margalida Rotger, Amalio Telenti, Yea Lih Lin, Philippe Pasero, Jonathan Maelfait, Michalis Titsias, Dena R. Cohen, Shirley J. Henderson, Mark T. Ross, David BentleyPeter Hillmen, Andrew Pettitt, Jan Rehwinkel, Samantha J.L. Knight, Jenny C. Taylor, Yanick J. Crow, Monsef Benkirane, Anna Schuh

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1021-1031
Number of pages	11
Journal	Blood
Volume	123
Issue number	7
DOIs	https://doi.org/10.1182/blood-2013-04-490847
Publication status	Published - 13 Feb 2014
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1182/blood-2013-04-490847

Cite this

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., ... Schuh, A. (2014). SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. Blood, 123(7), 1021-1031. https://doi.org/10.1182/blood-2013-04-490847

@article{1a26826227184c618c6395ea9718e9a6,

title = "SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage",

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-Gouti{\`e}res 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.",

author = "Ruth Clifford and Tania Louis and Pauline Robbe and Sam Ackroyd and Adam Burns and Timbs, {Adele T.} and {Wright Colopy}, Glen and Helene Dreau and Francois Sigaux and Judde, {Jean Gabriel} and Margalida Rotger and Amalio Telenti and Lin, {Yea Lih} and Philippe Pasero and Jonathan Maelfait and Michalis Titsias and Cohen, {Dena R.} and Henderson, {Shirley J.} and Ross, {Mark T.} and David Bentley and Peter Hillmen and Andrew Pettitt and Jan Rehwinkel and Knight, {Samantha J.L.} and Taylor, {Jenny C.} and Crow, {Yanick J.} and Monsef Benkirane and Anna Schuh",

year = "2014",

month = feb,

day = "13",

doi = "10.1182/blood-2013-04-490847",

language = "English",

volume = "123",

pages = "1021--1031",

journal = "Blood",

issn = "0006-4971",

number = "7",

}

Clifford, R, Louis, T, Robbe, P, Ackroyd, S, Burns, A, Timbs, AT, Wright Colopy, G, Dreau, H, Sigaux, F, Judde, JG, Rotger, M, Telenti, A, Lin, YL, Pasero, P, Maelfait, J, Titsias, M, Cohen, DR, Henderson, SJ, Ross, MT, Bentley, D, Hillmen, P, Pettitt, A, Rehwinkel, J, Knight, SJL, Taylor, JC, Crow, YJ, Benkirane, M & Schuh, A 2014, 'SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage', Blood, vol. 123, no. 7, pp. 1021-1031. https://doi.org/10.1182/blood-2013-04-490847

TY - JOUR

T1 - SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage

AU - Clifford, Ruth

AU - Louis, Tania

AU - Robbe, Pauline

AU - Ackroyd, Sam

AU - Burns, Adam

AU - Timbs, Adele T.

AU - Wright Colopy, Glen

AU - Dreau, Helene

AU - Sigaux, Francois

AU - Judde, Jean Gabriel

AU - Rotger, Margalida

AU - Telenti, Amalio

AU - Lin, Yea Lih

AU - Pasero, Philippe

AU - Maelfait, Jonathan

AU - Titsias, Michalis

AU - Cohen, Dena R.

AU - Henderson, Shirley J.

AU - Ross, Mark T.

AU - Bentley, David

AU - Hillmen, Peter

AU - Pettitt, Andrew

AU - Rehwinkel, Jan

AU - Knight, Samantha J.L.

AU - Taylor, Jenny C.

AU - Crow, Yanick J.

AU - Benkirane, Monsef

AU - Schuh, Anna

PY - 2014/2/13

Y1 - 2014/2/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84897585594&partnerID=8YFLogxK

U2 - 10.1182/blood-2013-04-490847

DO - 10.1182/blood-2013-04-490847

M3 - Article

C2 - 24335234

AN - SCOPUS:84897585594

SN - 0006-4971

VL - 123

SP - 1021

EP - 1031

JO - Blood

JF - Blood

IS - 7

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this