Rosati Emanuela, Baldoni Stefano, De Falco Filomena, Del Papa Beatrice, Dorillo Erica, Rompietti Chiara, Albi Elisa, Falzetti Franca, Di Ianni Mauro, Sportoletti Paolo
Department of Experimental Medicine, Biosciences and Medical Embryology Section, University of Perugia, Perugia, Italy.
Department of Life, Hematology Section, Health and Environmental Sciences, University of L'Aquila, Perugia, Italy.
Front Oncol. 2018 Jun 27;8:229. doi: 10.3389/fonc.2018.00229. eCollection 2018.
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 mutations in CLL. This review highlights recent discoveries that improve our understanding of the pathophysiological NOTCH1 signaling in CLL and the clinical impact of 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.
慢性淋巴细胞白血病（CLL）是一种无法治愈的B细胞肿瘤，其临床结局高度可变。近年来，基因组和分子研究揭示了CLL中存在显著的异质性，这反映了该疾病的临床多样性。这些研究极大地增进了我们对白血病细胞生物学的理解，并导致了具有潜在预后和治疗意义的新生物标志物的发现。越来越多的证据表明，NOTCH1信号失调和突变在CLL中起关键作用。本综述重点介绍了近期的发现，这些发现增进了我们对CLL中NOTCH1信号通路病理生理学的理解，以及回顾性和前瞻性试验中NOTCH1突变的临床影响。此外，我们讨论了针对CLL中NOTCH1信号通路抑制的治疗策略的基本原理，并概述了目前可用的针对NOTCH1的方法。
