title: Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia.
abstract: 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 select molecular lesions influencing outcome.
authors: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, Novara, Italy. rossidav@med.unipmn.it.
authors: Davide
authors: D
authors: Rossi
authors: Valeria
authors: V
authors: Spina
authors: Riccardo
authors: R
authors: Bomben
authors: Silvia
authors: S
authors: Rasi
authors: Michele
authors: M
authors: Dal-Bo
authors: Alessio
authors: A
authors: Bruscaggin
authors: Francesca Maria
authors: FM
authors: Rossi
authors: Sara
authors: S
authors: Monti
authors: Massimo
authors: M
authors: Degan
authors: Carmela
authors: C
authors: Ciardullo
authors: Roberto
authors: R
authors: Serra
authors: Antonella
authors: A
authors: Zucchetto
authors: Josep
authors: J
authors: Nomdedeu
authors: Pietro
authors: P
authors: Bulian
authors: Alberto
authors: A
authors: Grossi
authors: Francesco
authors: F
authors: Zaja
authors: Gabriele
authors: G
authors: Pozzato
authors: Luca
authors: L
authors: Laurenti
authors: Dimitar G
authors: DG
authors: Efremov
authors: Francesco
authors: F
authors: Di-Raimondo
authors: Roberto
authors: R
authors: Marasca
authors: Francesco
authors: F
authors: Forconi
authors: Giovanni
authors: G
authors: Del Poeta
authors: Gianluca
authors: G
authors: Gaidano
authors: Valter
authors: V
authors: Gattei
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D017354:Point Mutation; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D012189:Retrospective Studies; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D015996:Survival Rate
chemical_list: C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D011947:Receptors, Antigen, B-Cell; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human