1. A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression
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Pau Abrisqueta, Daniel Medina, Guillermo Villacampa, Junyan Lu, Miguel Alcoceba, Julia Carabia, Joan Boix, Barbara Tazón-Vega, Gloria Iacoboni, Sabela Bobillo, Ana Marín-Niebla, Marcos González, Thorsten Zenz, Marta Crespo, Francesc Bosch, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Junta de Castilla y León, Fundació La Marató de TV3, Institut Català de la Salut, [Abrisqueta P, Tazón-Vega B, Iacoboni G, Bobillo S, Marín-Niebla A, Bosch F] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Medina D, Carabia J, Boix J, Crespo M] Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Villacampa G] Oncology Data Science (OdysSey) Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Lu J] European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. [Alcoceba M, González M] Department of Hematology, University Hospital of Salamanca (HUS/IBSAL), CIBERONC and Center for Cancer Research-IBMCC (USAL-CSIC), Salamanca, Spain. [Zenz T] Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland, Vall d'Hebron Barcelona Hospital Campus, and University of Zurich
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Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment [PHENOMENA AND PROCESSES] ,Marcadors tumorals ,fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral [FENÓMENOS Y PROCESOS] ,610 Medicine & health ,Genetic Phenomena::Gene Expression [PHENOMENA AND PROCESSES] ,Hematology ,Prognosis ,Expressió gènica ,Leukemia, Lymphocytic, Chronic, B-Cell ,Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Leukemia, B-Cell::Leukemia, Lymphocytic, Chronic, B-Cell [DISEASES] ,10032 Clinic for Oncology and Hematology ,Mutation ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,Tumor Microenvironment ,Humans ,Leucèmia limfocítica crònica ,Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Transcriptome ,diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,fenómenos genéticos::expresión génica [FENÓMENOS Y PROCESOS] ,neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia de células B::leucemia linfocítica crónica de células B [ENFERMEDADES] ,Proportional Hazards Models - Abstract
Several gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P < .001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P = .007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P < .001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P < .001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression–based assay with prognostic implications in CLL., This work was supported by research funding from the Asociacion Espa ´ nola Contra el C ˜ ancer grant [5U01CA157581- 05, ECRIN-M3 - A29370] and in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00950, M.C., PI17/00943, F.B, PI18/01392, P.A.], and the Spanish Ministry of Economy and Competitiveness [CIBERONC-CB16/12/00233], the Education Council or Health Council of the Junta de Castilla y Leon [GRS 2036/A/19], and Gilead Sciences [GLD15/00348]. ´ This work was supported by research funding from the Asociacion´ Espanola Contra el C ˜ ancer grant [5U01CA157581-05, ECRIN-M3 ´ - A29370] and in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00950, M.C., PI17/00943, F.B, PI18/01392, P.A.], and the Spanish Ministry of Economy and Competitiveness [CIBERONC-CB16/12/00233], the Education Council or Health Council of the Junta de Castilla y Leon [GRS ´ 2036/A/19], Gilead Sciences [GLD15/00348] and Gilead Fellowships [GLD16/00144, GLD18/00047, F.B.], and Fundacio la ´Marato de TV3 [201905-30-31 F.B]. All Spanish funding was ´ cosponsored by the European Union FEDER program “Una manera de hacer Europa”. M.C. holds a contract from Ministerio de Ciencia, Innovacion y Universidades [RYC-2012-2018].
- Published
- 2022
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