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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rasi, S; Spina, V; Bruscaggin, A; Vaisitti, T; Tripodo, C; Forconi, F; De Paoli, L; Fangazio, M; Sozzi, E; Cencini, E; Laurenti, L; Marasca, R; Visco, C; Xu-Monette, ZY; Gattei, V; Young, KH; Malavasi, F; Deaglio, S; Gaidano, G; Rossi, D

Published Date

  • February 2011

Published In

Volume / Issue

  • 152 / 3

Start / End Page

  • 284 - 294

PubMed ID

  • 21121903

Pubmed Central ID

  • 21121903

Electronic International Standard Serial Number (EISSN)

  • 1365-2141

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2141.2010.08482.x


  • eng

Conference Location

  • England