NOTCH1 Aberrations in Chronic Lymphocytic Leukemia

被引：61
作者：
Rosati, Emanuela [1 ]
Baldoni, Stefano [2 ]
De Falco, Filomena [3 ]
Del Papa, Beatrice [3 ]
Dorillo, Erica [3 ]
Rompietti, Chiara [3 ]
Albi, Elisa [3 ]
Falzetti, Franca [3 ]
Di Ianni, Mauro [4 ,5 ]
Sportoletti, Paolo [3 ]
机构：
[1] Univ Perugia, Biosci & Med Embryol Sect, Dept Expt Med, Perugia, Italy
[2] Univ Aquila, Dept Life, Hematol Sect, Hlth & Environm Sci, Perugia, Italy
[3] Univ Perugia, CREO, Inst Hematol, Perugia, Italy
[4] Univ G dAnnunzio, Dept Med & Aging Sci, Chieti, Italy
[5] Osped Civile, Dept Hematol Transfus Med & Biotechnol, Pescara, Italy
来源：
FRONTIERS IN ONCOLOGY | 2018年 / 8卷
关键词：
NOTCH1; chronic lymphocytic leukemia; prognostic biomarker; targeted therapy; gene mutation; B-CELL-RECEPTOR; MARGINAL ZONE LYMPHOMA; PEST DOMAIN MUTATION; KAPPA-B; RECURRENT MUTATIONS; CLINICAL IMPACT; SF3B1; MUTATIONS; TP53; IN-VITRO; MOLECULAR PATHOGENESIS;
D O I：
10.3389/fonc.2018.00229
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Chronic lymphocytic leukemia (CLL) is an incurable B-cell neoplasm characterized by highly variable clinical outcomes. In recent years, genomic and molecular studies revealed a remarkable heterogeneity in CLL, which mirrored the clinical diversity of this disease. These studies profoundly enhanced our understanding of leukemia cell biology and led to the identification of new biomarkers with potential prognostic and therapeutic significance. Accumulating evidence indicates a key role of deregulated NOTCH1 signaling and NOTCH1 mutations in CLL. This review highlights recent discoveries that improve our understanding of the pathophysiological NOTCH1 signaling in CLL and the clinical impact of NOTCH1 mutations in retrospective and prospective trials. In addition, we discuss the rationale for a therapeutic strategy aiming at inhibiting NOTCH1 signaling in CLL, along with an overview on the currently available NOTCH1-directed approaches.
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页数：20
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