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

Luca Laurenti, S Rasi, V Spina, A Bruscaggin, T Vaisitti, C Tripodo, F Forconi, L De Paoli, M Fangazio, E Sozzi, E Cencini, R Marasca, C Visco, Zy Xu Monette, V Gattei, Kh Young, F Malavasi, S Deaglio, G Gaidano, D. Rossi

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25 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)284-294
Number of pages11
JournalBritish Journal of Haematology
Publication statusPublished - 2011


  • Aged
  • Amino Acid Sequence
  • Animals
  • Disease Progression
  • Epidemiologic Methods
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • LDL-Receptor Related Proteins
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Sequence Alignment
  • Syndrome


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