Association between molecular lesions and specific B-cell receptor subsets in chronic lymphocytic leukemia

被引：109

作者：

Rossi, Davide ^{[1
]}

Spina, Valeria ^{[1
]}

Bomben, Riccardo ^{[2
]}

Rasi, Silvia ^{[1
]}

Dal-Bo, Michele ^{[2
]}

Bruscaggin, Alessio ^{[1
]}

Rossi, Francesca Maria ^{[2
]}

Monti, Sara ^{[1
]}

Degan, Massimo ^{[2
]}

Ciardullo, Carmela ^{[1
]}

Serra, Roberto ^{[3
]}

Zucchetto, Antonella ^{[2
]}

Nomdedeu, Josep ^{[4
]}

Bulian, Pietro ^{[2
]}

Grossi, Alberto

Zaja, Francesco ^{[5
]}

Pozzato, Gabriele ^{[6
]}

Laurenti, Luca ^{[7
]}

Efremov, Dimitar G. ^{[8
]}

Di-Raimondo, Francesco ^{[9
]}

Marasca, Roberto ^{[10
]}

Forconi, Francesco ^{[11
,12
]}

Del Poeta, Giovanni ^{[13
]}

Gaidano, Gianluca ^{[1
]}

Gattei, Valter ^{[2
]}

机构：

[1] Amedeo Avogadro Univ Eastern Piedmont, Div Hematol, Dept Translat Med, I-28100 Novara, Italy

[2] Ctr Riferimento Oncol, I-33081 Aviano, Italy

[3] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Lab Med Informat, Novara, Italy

[4] Hosp Santa Creu & Sant Pau, Dept Hematol & Lab, Barcelona, Spain

[5] Azienda Osped Univ SM Misericordia, Ctr Trapianti & Terapie Cellulari Carlo Melzi, Dipartimento Sci Med Sperimentali & Clin, Udine, Italy

[6] Maggiore Hosp, Dept Internal Med & Haematol, Trieste, Italy

[7] Univ Cattolica Sacro Cuore, Inst Hematol, I-00168 Rome, Italy

[8] Int Ctr Genet Engn & Biotechnol, Rome, Italy

[9] Univ Catania, Sect Hematol Oncol & Clin Pathol, Dept Clin & Mol Biomed, Catania, Italy

[10] Univ Modena & Reggio Emilia, Dept Hematol & Oncol, Div Hematol, Modena, Italy

[11] Univ Southampton, Canc Res UK Clin Ctr, Canc Sci Unit, Southampton, Hants, England

[12] Univ Siena, Div Hematol, I-53100 Siena, Italy

[13] Univ Roma Tor Vergata, Dept Hematol, Rome, Italy

来源：

BLOOD | 2013年 / 121卷 / 24期

关键词：

NOTCH1; MUTATIONS; SF3B1; TRANSFORMATION; PATTERNS; RISK; CLL;

D O I：

10.1182/blood-2013-02-486209

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：4902 / 4905

页数：4

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