Next-generation sequencing in chronic lymphocytic leukemia: recent findings and new horizons

The rapid progress in next-generation sequencing technologies has significantly contributed to our knowledge of the genetic events associated with the development, progression and treatment resistance of chronic lymphocytic leukemia patients. Together with the discovery of new driver mutations, next-generation sequencing has revealed an immense degree of both intra- and inter-tumor heterogeneity and enabled us to describe marked clonal evolution. Advances in immunogenetics may be implemented to detect minimal residual disease more sensitively and to track clonal B cell populations, their dynamics and molecular characteristics. The interpretation of these aspects is indispensable to thoroughly examine the genetic background of chronic lymphocytic leukemia. We review and discuss the recent results provided by the different next-generation sequencing techniques used in studying the chronic lymphocytic leukemia genome, as well as future perspectives in the methodologies and applications.This work received funding from the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement n°306242-NGS-PTL and MSMT CR (2013–2015/no.7E13008). It was also supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI12/00281 and PI15/01471, Proyectos de Investigación del SACYL 355/A/09, COST Action EuGESMA (BM0801), Fundación Manuel Solórzano, Obra Social Banca Cívica (Caja Burgos), Fundación Española de Hematología y Hemoterapia (FEHH), and by grants (RD12/0036/0069 and RD12/0036/0044) from the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness and European Regional Development Fund (ERDF) “Una manera de hacer Europa” (CEI 2010-1-0010). AERV is supported by a grant from the Fundación Ramón Areces. MHS is fully supported by an Ayuda Predoctoral de la Junta de Castilla y León from the Fondo Social Europeo (JCYL-EDU/346/2013 PhD scholarship). SP, VB and JM were supported by AZV grants from the Ministry of Health of the Czech Republic No. 15-31834A, 15-30015A and 16-29447A, MH CR project 65269705 and MSMT CR project CEITEC2020 LQ1601 under the National Sustainability Programme II.Peer Reviewe