title: Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome.
abstract: OBJECTIVE
  Few biological prognosticators are useful for prediction of Richter syndrome (RS), representing the transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. Stereotyped B-cell receptors (BCR) may have prognostic effect in CLL progression. We tested the prognostic effect of stereotyped BCR for predicting RS transformation.
  
  
  METHODS
  The prevalence of stereotyped BCR was compared in RS (n = 69) versus nontransformed CLL (n = 714) by a case-control analysis. Subsequently, the effect of stereotyped BCR at CLL diagnosis on risk of RS transformation was actuarially assessed in a consecutive CLL series (n = 753).
  
  
  RESULTS
  RS (n = 69) displayed a higher prevalence of stereotyped BCR (P < 0.001) compared with nontransformed CLL. The actuarial risk of RS transformation was significantly higher in CLL carrying stereotyped BCR (P < 0.001). Among BCR subsets most represented in CLL, subset 8 using IGHV4-39/IGHD6-13/IGHJ5 carried the highest risk of RS transformation [hazard ratio (HR), 24.50; P < 0.001]. Multivariate analysis selected stereotyped BCR (HR, 3.33; P = 0.001) and IGHV4-39 usage (HR, 4.03; P = 0.004) as independent predictors of RS transformation. The combination of IGHV4-39 usage and stereotyped BCR in the same patient identified CLL with a very high risk of RS transformation (5-year risk, 68.7%). The risk carried by stereotyped BCR and IGHV4-39 usage was specific for RS transformation and had no effect on CLL progression without transformation.
  
  
  CONCLUSIONS
  Analysis of BCR features may help identify CLL patients at risk of RS. A close monitoring and a careful biopsy policy may help early recognition of RS in CLL patients using stereotyped BCR, particularly if combined with IGHV4-39.
authors.affiliation: Amedeo Avogadro University of Eastern Piedmont, Novara, Italy. rossidav@med.unipmn.it
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Valeria
authors.initials: V
authors.lastname: Spina
authors.forename: Michaela
authors.initials: M
authors.lastname: Cerri
authors.forename: Silvia
authors.initials: S
authors.lastname: Rasi
authors.forename: Clara
authors.initials: C
authors.lastname: Deambrogi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: De Paoli
authors.forename: Luca
authors.initials: L
authors.lastname: Laurenti
authors.forename: Rossana
authors.initials: R
authors.lastname: Maffei
authors.forename: Francesco
authors.initials: F
authors.lastname: Forconi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zucca
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.forename: Antonello
authors.initials: A
authors.lastname: Cabras
authors.forename: Marco
authors.initials: M
authors.lastname: Lucioni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.forename: Michele
authors.initials: M
authors.lastname: Magni
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedeu
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.forename: Antonio
authors.initials: A
authors.lastname: Ramponi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.forename: Marco
authors.initials: M
authors.lastname: Paulli
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Larocca
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Valter
authors.initials: V
authors.lastname: Gattei
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
mesh_terms: D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011110:Polymorphism, Genetic / Q000502:physiology; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics / Q000502:physiology*; D012307:Risk Factors; D013577:Syndrome
chemical_list: C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr