Stereotyped B-cell receptor is an independent risk factor of chronic lymphocytic leukemia transformation to Richter syndrome.
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.
Rossi
Davide
D
Amedeo Avogadro University of Eastern Piedmont, Novara, Italy. rossidav@med.unipmn.it
Spina
Valeria
V
Cerri
Michaela
M
Rasi
Silvia
S
Deambrogi
Clara
C
De Paoli
Lorenzo
L
Laurenti
Luca
L
Maffei
Rossana
R
Forconi
Francesco
F
Bertoni
Francesco
F
Zucca
Emanuele
E
Agostinelli
Claudio
C
Cabras
Antonello
A
Lucioni
Marco
M
Martini
Maurizio
M
Magni
Michele
M
Deaglio
Silvia
S
Ladetto
Marco
M
Nomdedeu
Josep F
JF
Besson
Caroline
C
Ramponi
Antonio
A
Canzonieri
Vincenzo
V
Paulli
Marco
M
Marasca
Roberto
R
Larocca
Luigi M
LM
Carbone
Antonino
A
Pileri
Stefano A
SA
Gattei
Valter
V
Gaidano
Gianluca
G
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
C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr