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La Carta Medellín fue el documento oficial de conclusiones que quedó como testimonio de las sesiones correspondientes al Séptimo Foro Urbano Mundial que tuvo lugar en Medellín entre el 5 y el 9 de abril pasados, organizado por ONU-Hábitat en alianza con la Alcaldía de Medellín y el Ministerio de la vivienda. El texto de 170 páginas, se supone, recoge los insumos más importantes de los diálogos, asambleas y mesas redondas que tuvieron lugar en el marco de ese imponente evento que movilizó decenas de miles de visitantes y millones de dólares en financiación.

El marketing político es concebido como una práctica para estudiar, satisfacer y gestionar las demandas del mercado electoral, desde dicho punto de vista, se hace pertinente examinar las relaciones entre dicho fenómeno y el concepto de comunidades de marca debido a su especial trascendencia para la gestión con militantes a partir de características y valores comunes. Para tal fin, este estudio investigo la relación entre dichas variables. Se empleó un diseño descriptivo relacional a partir de un muestreo no probabilístico por cuotas con 384 militantes. Los hallazgos sugieren rasgos determinantes que caracterizan a estas comunidades políticas presentes en Bogotá, D.C. ; Political marketing is conceived as a practice to study, meet and manage the demands of the electoral market, from that point of view, it becomes relevant to examine the relationship between this phenomenon and the concept of brand communities because of their special importance for the management with militants from characteristics and common values. To this end, this study investigated the relationship between these variables. A relational descrip­tive design from a non-probability quota sampling was used with 384 militants. The findings suggest determining features that characterize these political communities in Bogotá, DC ; O marketing político é concebido como uma prática para estudar, satisfazer e gerir as deman­das do mercado eleitoral, desde dito ponto de vista, se faz pertinente examinar as relações entre dito fenômeno e o conceito de comunidades de marca devido à sua especial transcen­dência para a gestão com militantes a partir de características e valores comuns. Para tal fim, este estudo investigou a relação entre ditas variáveis. Empregou-se um desenho descritivo relacional a partir de uma amostragem probabilística por cotas com 384 militantes. Os acha­dos sugerem rasgos determinantes que caracterizam a estas comunidades políticas presentes em Bogotá, D.C.

El marketing político es concebido como una práctica para estudiar, satisfacer y gestionar las demandas del mercado electoral, desde dicho punto de vista, se hace pertinente examinar las relaciones entre dicho fenómeno y el concepto de comunidades de marca debido a su especial trascendencia para la gestión con militantes a partir de características y valores comunes. Para tal fin, este estudio investigo la relación entre dichas variables. Se empleó un diseño descriptivo relacional a partir de un muestreo no probabilístico por cuotas con 384 militantes. Los hallazgos sugieren rasgos determinantes que caracterizan a estas comunidades políticas presentes en Bogotá, D.C. ; O marketing político é concebido como uma prática para estudar, satisfazer e gerir as deman­das do mercado eleitoral, desde dito ponto de vista, se faz pertinente examinar as relações entre dito fenômeno e o conceito de comunidades de marca devido à sua especial transcen­dência para a gestão com militantes a partir de características e valores comuns. Para tal fim, este estudo investigou a relação entre ditas variáveis. Empregou-se um desenho descritivo relacional a partir de uma amostragem probabilística por cotas com 384 militantes. Os acha­dos sugerem rasgos determinantes que caracterizam a estas comunidades políticas presentes em Bogotá, D.C. ; Political marketing is conceived as a practice to study, meet and manage the demands of the electoral market, from that point of view, it becomes relevant to examine the relationship between this phenomenon and the concept of brand communities because of their special importance for the management with militants from characteristics and common values. To this end, this study investigated the relationship between these variables. A relational descrip­tive design from a non-probability quota sampling was used with 384 militants. The findings suggest determining features that characterize these political communities in Bogotá, DC

Karl R. Popper es uno de los principales exponentes de la filosofía contemporánea; se destaca por su contribución a la epistemología y por su defensa de la democracia. El presente artículo reconstruye un seminario realizado sobre su pensamiento como un primer acercamiento a su planteamiento epistemológico; además constituye un avance de carácter bibliográfico que servirá de base para explicitar la Teoría Educativa del Racionalismo Crítico.

Karl R. Popper es uno de los principales exponentes de la filosofía contemporánea; se destaca por su contribución a la epistemología y por su defensa de la democracia. El presente artículo reconstruye un seminario realizado sobre su pensamiento como un primer acercamiento a su planteamiento epistemológico; además constituye un avance de carácter bibliográfico que servirá de base para explicitar la Teoría Educativa del Racionalismo Crítico. DOI: http://dx.doi.org/10.22518/16578953.788

El emprendimiento es una actividad generadora de riqueza, puesto que el conocimiento, la creatividad y la innovación de ideas emprendedoras, beneficiarán la sociedad y a su vez al sector productivo. Por medio de una revisión de la literatura se reconoce la evolución de los procesos emprendedores en Colombia y su incidencia en sus sectores productivos.
Se evidencia que el sector con menor stock de empresas es el de construcción y el de mayor corresponde al sector de comercio, el sector servicios es el de mayor volatilidad, mientras que el sector industria es el más estático. Los servicios comienzan a tener un descenso paulatino frente al desarrollo de emprendimientos futuros, siendo el consumo el sector clave en términos creación de empresas para el contexto colombiano.

Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data. ; F.M. is supported by A.I.L. (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS), by S.I.E.S. (Società Italiana di Ematologia Sperimentale) and by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748). N.B. is funded by the University of Milan (project 22597-PSR2017_DIP_032) and by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 817997). X.S.P. is supported by thr Ministerio de Economía y Competitividad Grant No. SAF2017–87811-R. F.N. is supported by a pre-doctoral fellowship of the MINECO (BES-2016–076372). This work was supported by the Instituto de Salud Carlos III (project PMP15/00007, F.N., E.C.), the "la Caixa" Foundation Grant No HR17-00221 (Health Research 2017 Program, F.N., E.C.), the Ministerio de Economía y Competitividad (MINECO) SAF2013-45836-R (E.C.) from. Plan Nacional de I + D + I, Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-1142 (E.C.) and the European Regional Development Fund "Una manera de hacer Europa". E.C. is supported by ICREA under the ICREA Academia program. A.D. is funded by a CRUK Pioneer Award C60100/A23433. S.N.Z. is funded by a CRUK Advanced Clinician Scientist Award (C60100/A23916) and a CRUK Grand Challenge Award (C60100/A25274). This work was supported by: Department of Veterans Affairs Merit Review Award I01BX001584-01 (N.C.M.), NIH grants P01-155258 (N.C.M., H.A.L., M.F., P.J.C., K.C.A.) and 5P50CA100707-13 (N.C.M., H.A.L., K.C.A).

Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data. ; F.M. is supported by A.I.L. (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS), by S.I.E.S. (Società Italiana di Ematologia Sperimentale) and by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748). N.B. is funded by the University of Milan (project 22597-PSR2017_DIP_032) and by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 817997). X.S.P. is supported by thr Ministerio de Economía y Competitividad Grant No. SAF2017–87811-R. F.N. is supported by a pre-doctoral fellowship of the MINECO (BES-2016–076372). This work was supported by the Instituto de Salud Carlos III (project PMP15/00007, F.N., E.C.), the "la Caixa" Foundation Grant No HR17-00221 (Health Research 2017 Program, F.N., E.C.), the Ministerio de Economía y Competitividad (MINECO) SAF2013-45836-R (E.C.) from. Plan Nacional de I + D + I, Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-1142 (E.C.) and the European Regional Development Fund "Una manera de hacer Europa". E.C. is supported by ICREA under the ICREA Academia program. A.D. is funded by a CRUK Pioneer Award C60100/A23433. S.N.Z. is funded by a CRUK Advanced Clinician Scientist Award (C60100/A23916) and a CRUK Grand Challenge Award (C60100/A25274). This work was supported by: Department of Veterans Affairs Merit Review Award I01BX001584-01 (N.C.M.), NIH grants P01-155258 (N.C.M., H.A.L., M.F., P.J.C., K.C.A.) and 5P50CA100707-13 (N.C.M., H.A.L., K.C.A). We thank Michael R. Stratton for discussions and help in data interpretation. ; Peer Reviewed ; Postprint (author's final draft)

Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data. ; F.M. is supported by A.I.L. (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS), by S.I.E.S. (Società Italiana di Ematologia Sperimentale) and by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748). N.B. is funded by the University of Milan (project 22597-PSR2017_DIP_032) and by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 817997). X.S.P. is supported by thr Ministerio de Economía y Competitividad Grant No. SAF2017–87811-R. F.N. is supported by a pre-doctoral fellowship of the MINECO (BES-2016–076372). This work was supported by the Instituto de Salud Carlos III (project PMP15/00007, F.N., E.C.), the "la Caixa" Foundation Grant No HR17-00221 (Health Research 2017 Program, F.N., E.C.), the Ministerio de Economía y Competitividad (MINECO) SAF2013-45836-R (E.C.) from. Plan Nacional de I + D + I, Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-1142 (E.C.) and the European Regional Development Fund "Una manera de hacer Europa". E.C. is supported by ICREA under the ICREA Academia program. A.D. is funded by a CRUK Pioneer Award C60100/A23433. S.N.Z. is funded by a CRUK Advanced Clinician Scientist Award (C60100/A23916) and a CRUK Grand Challenge Award (C60100/A25274). This work was supported by: Department of Veterans Affairs Merit Review Award I01BX001584-01 (N.C.M.), NIH grants P01-155258 (N.C.M., H.A.L., M.F., P.J.C., K.C.A.) and 5P50CA100707-13 (N.C.M., H.A.L., K.C.A). We thank Michael R. Stratton for discussions and help in data interpretation. ; Peer Reviewed ; Postprint (author's final draft)

Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, prognosis, and even treatment decisions. However, the field lacks a consensus on analysis and result interpretation. Using whole-genome sequencing of multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and acute myeloid leukemia, we compare the performance of public signature analysis tools. We describe caveats and pitfalls of de novo signature extraction and fitting approaches, reporting on common inaccuracies: erroneous signature assignment, identification of localized hyper-mutational processes, overcalling of signatures. We provide reproducible solutions to solve these issues and use orthogonal approaches to validate our results. We show how a comprehensive mutational signature analysis may provide relevant biological insights, reporting evidence of c-AID activity among unmutated CLL cases or the absence of BRCA1/BRCA2-mediated homologous recombination deficiency in a MM cohort. Finally, we propose a general analysis framework to ensure production of accurate and reproducible mutational signature data. ; F.M. is supported by A.I.L. (Associazione Italiana Contro le Leucemie-Linfomi e Mieloma ONLUS), by S.I.E.S. (Società Italiana di Ematologia Sperimentale) and by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748). N.B. is funded by the University of Milan (project 22597-PSR2017_DIP_032) and by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 817997). X.S.P. is supported by thr Ministerio de Economía y Competitividad Grant No. SAF2017–87811-R. F.N. is supported by a pre-doctoral fellowship of the MINECO (BES-2016–076372). This work was supported by the Instituto de Salud Carlos III (project PMP15/00007, F.N., E.C.), the "la Caixa" Foundation Grant No HR17-00221 (Health Research 2017 Program, F.N., E.C.), the Ministerio de Economía y Competitividad (MINECO) SAF2013-45836-R (E.C.) from. Plan Nacional de I + D + I, Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-1142 (E.C.) and the European Regional Development Fund "Una manera de hacer Europa". E.C. is supported by ICREA under the ICREA Academia program. A.D. is funded by a CRUK Pioneer Award C60100/A23433. S.N.Z. is funded by a CRUK Advanced Clinician Scientist Award (C60100/A23916) and a CRUK Grand Challenge Award (C60100/A25274). This work was supported by: Department of Veterans Affairs Merit Review Award I01BX001584-01 (N.C.M.), NIH grants P01-155258 (N.C.M., H.A.L., M.F., P.J.C., K.C.A.) and 5P50CA100707-13 (N.C.M., H.A.L., K.C.A). We thank Michael R. Stratton for discussions and help in data interpretation.

Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. We used a platform for drug discovery based on systems biology and artificial intelligence, to identify drugs targeting key proteins described to have a role in the microenvironment. The selected compounds were screened in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. We proposed that systems biology approaches combined with pharmacological screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells. ; The study was supported by research funding from the Spanish Ministry of Economy and Competitiveness through the Plan Estatal de Investigación Científica y Técnica y de Innovación (MINECO) RTI2018-094584-B-I00 [to DC] and was cofunded by the European Regional Development Fund [ERDF] and the CERCA program from Generalitat de Catalunya, Centro de Investigación Biomédica en Cáncer [CIBERONC] [CB16/12/00334 and CB16/12/00225] and Generalitat de Catalunya Suport Grups de Recerca [2017 SGR 1009]. This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 306240. NG is a recipient of ...

Robust protocols and automation now enable large-scale single-cell RNA and ATAC sequencing experiments and their application on biobank and clinical cohorts. However, technical biases introduced during sample acquisition can hinder solid, reproducible results, and a systematic benchmarking is required before entering large-scale data production. Here, we report the existence and extent of gene expression and chromatin accessibility artifacts introduced during sampling and identify experimental and computational solutions for their prevention. ; HH is a Miguel Servet (CP14/00229) researcher funded by the Spanish Institute of Health Carlos III (ISCIII). CM and MK are supported by AECC postdoctoral fellowships. This work has received funding from the Ministerio de Ciencia, Innovación y Universidades (SAF2017-89109-P; AEI/FEDER, UE). This study was further funded by the Spanish Ministry of Economy and Competitiveness (grant number: IPT-010000-2010- 36, cofunded by the European Regional Development Fund). Core funding is from the ISCIII and the Generalitat de Catalunya. We acknowledge support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa, the CERCA Programme/Generalitat de Catalunya, the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) through the Instituto de Salud Carlos III and the Generalitat de Catalunya through Departament de Salut and Departament d'Empresa i Coneixement. We also acknowledge the Co-financing by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) with funds from the European Regional Development Fund (ERDF) corresponding to the 2014–2020 Smart Growth Operating Program. We acknowledge the Generalitat de Catalunya Suport Grups de Recerca AGAUR 2017-SGR-736 (to JIMS) and 2017-SGR-1142 (to EC), and CIBERONC (CB16/12/00225 and CB16/12/00334). EC is an ICREA Academia Researcher. This project received support from the European Commission under the projects DocTIS (H2020, SEP-210574908). This publication is part of a project (BCLLATLAS) that has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 810287)

Background: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. Methods: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. Results: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. Conclusions: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia ; This work was supported by the "Acción Transversal del Cancer", approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III (Spanish Government) (grants PI08/1770, PI08/0533, PI08/ 1359, PS09/00773-Cantabria, PI11/01810, PI11/02213, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RTIC RD12/0036/0056, Rio Hortega CM13/ 00232, SV-09-CLINIC-1 and CIBERESP), by the Fundación Marques de Valdecilla (API 10/09), by Obra Social CAJASTUR (SV-CAJASTUR-1), by the Recercaixa (2010ACUP 00310), by the Spanish Association Against Cancer (AECC) Scientific Foundation and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)–Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2009SGR1026, 2014SGR756 and 2009SGR1465). The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTIC RD12/0036/0036) del ISCIII. Sample collection and storage was partially supported by the Instituto de Salud Carlos III FEDER (RD09/0076/00036), Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC).

BACKGROUND: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. METHODS: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. RESULTS: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. CONCLUSIONS: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia. ; This work was supported by the "Acción Transversal del Cancer", approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III (Spanish Government) (grants PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PI11/01810, PI11/02213, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RTIC RD12/0036/0056, Rio Hortega CM13/00232, SV-09-CLINIC-1 and CIBERESP), by the Fundación Marques de Valdecilla (API 10/09), by Obra Social CAJASTUR (SV-CAJASTUR-1), by the Recercaixa (2010ACUP 00310), by the Spanish Association Against Cancer (AECC) Scientific Foundation and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)–Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2009SGR1026, 2014SGR756 and 2009SGR1465). The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTIC RD12/0036/0036) del ISCIII. Sample collection and storage was partially supported by the Instituto de Salud Carlos III FEDER (RD09/0076/00036), Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC). ; Sí