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A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome

A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome
A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome
Richter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty-five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047). The enrichment of LRP4 TT genotype in RS was confirmed in an independent series (n = 44) used for validation purposes. The LRP4 protein was expressed in CLL (n =66). Bioinformatic analysis scored LRP4 rs2306029 as a variant with possible deleterious and damaging variant of LRP4. LRP4 genotyping may help the recognition of patients with increased risk of RS at the time of CLL diagnosis.
richter syndrome, chronic lymphocytic leukaemia, diffuse large b cell lymphoma, single nucleotide polimorphism, LRP4
0007-1048
284-294
Rasi, Silvia
13639ced-c17f-4350-87e4-fb670cee592b
Spina, Valeria
bb72602d-3d56-424f-b169-47377aef1d10
Bruscaggin, Alessio
0a5ac2c3-9c5d-489c-8e5f-bb108166da61
Vaisitti, Tiziana
91a979a2-450f-4a33-ae43-8634908a2f56
Tripodo, Claudio
5c73a8cd-61c1-4521-a48c-6a15c4cec17b
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
De Paoli, Lorenzo
9390755d-1a39-47e9-bc54-69f9fe914248
Fangazio, Marco
054da702-e7e5-4721-84f6-c0cca9abd043
Sozzi, Elisa
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Cencini, Emanuele
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Laurenti, Luca
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Marasca, Roberto
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Visco, Carlo
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Xu-Monette, Zijun Y.
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Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Young, Ken H.
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Malavasi, Fabio
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Deaglio, Silvia
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Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Rossi, Davide
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Rasi, Silvia
13639ced-c17f-4350-87e4-fb670cee592b
Spina, Valeria
bb72602d-3d56-424f-b169-47377aef1d10
Bruscaggin, Alessio
0a5ac2c3-9c5d-489c-8e5f-bb108166da61
Vaisitti, Tiziana
91a979a2-450f-4a33-ae43-8634908a2f56
Tripodo, Claudio
5c73a8cd-61c1-4521-a48c-6a15c4cec17b
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
De Paoli, Lorenzo
9390755d-1a39-47e9-bc54-69f9fe914248
Fangazio, Marco
054da702-e7e5-4721-84f6-c0cca9abd043
Sozzi, Elisa
e811ff23-6fe9-47ec-b052-fe8d34d1e36b
Cencini, Emanuele
3dc5d188-96b0-4f7d-abb8-af4d22638d7e
Laurenti, Luca
23c6052d-80af-4fac-92da-2a495a8cb440
Marasca, Roberto
918148d0-8f99-4a29-8322-1b34f6d7dd00
Visco, Carlo
2c102cee-f0d7-4738-9cd9-ca366c735c1b
Xu-Monette, Zijun Y.
b95fc77d-ca74-4d03-bb68-2cfd24f0ee57
Gattei, Valter
df828ae8-1b40-4acb-8908-5a6b3d16cf99
Young, Ken H.
12c14059-62da-47b2-9bfb-f05c6a363c70
Malavasi, Fabio
3c9e22c9-bc60-4824-8c4b-392b9554bfcd
Deaglio, Silvia
2e20f72c-3eb1-4388-a371-8cace561211c
Gaidano, Gianluca
1a6a7107-107b-4891-82e0-5fedadd2f65a
Rossi, Davide
b4b2506d-794c-4c79-8b2d-6767554fd52a

Rasi, Silvia, Spina, Valeria, Bruscaggin, Alessio, Vaisitti, Tiziana, Tripodo, Claudio, Forconi, Francesco, De Paoli, Lorenzo, Fangazio, Marco, Sozzi, Elisa, Cencini, Emanuele, Laurenti, Luca, Marasca, Roberto, Visco, Carlo, Xu-Monette, Zijun Y., Gattei, Valter, Young, Ken H., Malavasi, Fabio, Deaglio, Silvia, Gaidano, Gianluca and Rossi, Davide (2011) A variant of the LRP4 gene affects the risk of chronic lymphocytic leukaemia transformation to Richter syndrome. British Journal of Haematology, 152 (3), 284-294. (doi:10.1111/j.1365-2141.2010.08482.x). (PMID:21121903)

Record type: Article

Abstract

Richter syndrome (RS) represents the transformation of chronic lymphocytic leukaemia (CLL) to aggressive lymphoma. Risk factors of CLL transformation to RS are only partly known. We explored the role of the host genetic background as a risk factor for RS occurrence. Forty-five single nucleotide polimorphisms (SNPs) known to be relevant for CLL prognosis were genotyped in a consecutive cohort of 331 CLL, of which 21 had transformed to RS. After correcting for multiple testing and adjusting for previously reported RS risk factors, the LRP4 rs2306029 TT variant genotype was the sole SNP independently associated with a higher risk of RS transformation (Hazard Ratio: 4·17; P = 0·001; q = 0·047). The enrichment of LRP4 TT genotype in RS was confirmed in an independent series (n = 44) used for validation purposes. The LRP4 protein was expressed in CLL (n =66). Bioinformatic analysis scored LRP4 rs2306029 as a variant with possible deleterious and damaging variant of LRP4. LRP4 genotyping may help the recognition of patients with increased risk of RS at the time of CLL diagnosis.

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More information

e-pub ahead of print date: 1 December 2010
Published date: February 2011
Keywords: richter syndrome, chronic lymphocytic leukaemia, diffuse large b cell lymphoma, single nucleotide polimorphism, LRP4
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 358134
URI: http://eprints.soton.ac.uk/id/eprint/358134
ISSN: 0007-1048
PURE UUID: 51a881c2-062b-46ea-af32-77228f215c39
ORCID for Francesco Forconi: ORCID iD orcid.org/0000-0002-2211-1831

Catalogue record

Date deposited: 08 Oct 2013 11:12
Last modified: 15 Mar 2024 03:41

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Contributors

Author: Silvia Rasi
Author: Valeria Spina
Author: Alessio Bruscaggin
Author: Tiziana Vaisitti
Author: Claudio Tripodo
Author: Lorenzo De Paoli
Author: Marco Fangazio
Author: Elisa Sozzi
Author: Emanuele Cencini
Author: Luca Laurenti
Author: Roberto Marasca
Author: Carlo Visco
Author: Zijun Y. Xu-Monette
Author: Valter Gattei
Author: Ken H. Young
Author: Fabio Malavasi
Author: Silvia Deaglio
Author: Gianluca Gaidano
Author: Davide Rossi

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