TY - JOUR
T1 - Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia
AU - Rossi, Davide
AU - Spina, Valeria
AU - Bomben, Riccardo
AU - Rasi, Silvia
AU - Dal-Bo, Michele
AU - Bruscaggin, Alessio
AU - Rossi, Francesca Maria
AU - Monti, Sara
AU - Degan, Massimo
AU - Ciardullo, Carmela
AU - Serra, Roberto
AU - Zucchetto, Antonella
AU - Nomdedeu, Josep
AU - Bulian, Pietro
AU - Grossi, Alberto
AU - Zaja, Francesco
AU - Pozzato, Gabriele
AU - Laurenti, Luca
AU - Efremov, Dimitar G.
AU - Di-Raimondo, Francesco
AU - Marasca, Roberto
AU - Forconi, Francesco
AU - Del Poeta, Giovanni
AU - Gaidano, Gianluca
AU - Gattei, Valter
PY - 2013/6/13
Y1 - 2013/6/13
N2 - Genetic lesions and B-cell receptor (BCR) signaling are both oncogenic drivers in chronic lymphocytic leukemia (CLL). However, scant data are available on preferential associations between specific genetic alterations and stereotyped BCR subsets. By analyzing 1419 cases, 2 CLL subsets (2 and 8) harboring stereotyped BCR are enriched in specific molecular alterations influencing disease course. SF3B1 mutations are the genetic hallmark of IGHV3-21-CLL belonging to subset 2 (52%) but are evenly represented in nonstereotyped IGHV3-21-CLL. Trisomy 12 (87%) and NOTCH1 mutations (62%) characterize IGHV4-39-CLL belonging to subset 8 but occur with the expected frequency in IGHV4-39-CLL with heterogeneous BCR. Clinically, co-occurrence of SF3B1 mutations and subset 2 BCR configuration prompts disease progression in IGHV3-21-CLL, whereas cooperation between NOTCH1 mutations, +12, and subset 8 BCR configuration invariably primes CLL transformation into Richter syndrome. These findings provide a proof of concept that specific stereotyped BCR may promote or selectmolecular lesions influencing outcome.
AB - Genetic lesions and B-cell receptor (BCR) signaling are both oncogenic drivers in chronic lymphocytic leukemia (CLL). However, scant data are available on preferential associations between specific genetic alterations and stereotyped BCR subsets. By analyzing 1419 cases, 2 CLL subsets (2 and 8) harboring stereotyped BCR are enriched in specific molecular alterations influencing disease course. SF3B1 mutations are the genetic hallmark of IGHV3-21-CLL belonging to subset 2 (52%) but are evenly represented in nonstereotyped IGHV3-21-CLL. Trisomy 12 (87%) and NOTCH1 mutations (62%) characterize IGHV4-39-CLL belonging to subset 8 but occur with the expected frequency in IGHV4-39-CLL with heterogeneous BCR. Clinically, co-occurrence of SF3B1 mutations and subset 2 BCR configuration prompts disease progression in IGHV3-21-CLL, whereas cooperation between NOTCH1 mutations, +12, and subset 8 BCR configuration invariably primes CLL transformation into Richter syndrome. These findings provide a proof of concept that specific stereotyped BCR may promote or selectmolecular lesions influencing outcome.
UR - http://www.scopus.com/inward/record.url?scp=84881266955&partnerID=8YFLogxK
U2 - 10.1182/blood-2013-02-486209
DO - 10.1182/blood-2013-02-486209
M3 - Article
SN - 0006-4971
VL - 121
SP - 4902
EP - 4905
JO - Blood
JF - Blood
IS - 24
ER -