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World J Clin Oncol. Apr 24, 2023; 14(4): 160-170
Published online Apr 24, 2023. doi: 10.5306/wjco.v14.i4.160
Integration of molecular testing for the personalized management of patients with diffuse large B-cell lymphoma and follicular lymphoma
Ruth Stuckey, Hugo Luzardo Henríquez, Haridian de la Nuez Melian, José Carlos Rivero Vera, Cristina Bilbao-Sieyro, María Teresa Gómez-Casares
Ruth Stuckey, Hugo Luzardo Henríquez, Haridian de la Nuez Melian, Department of Hematology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas 35019, Spain
José Carlos Rivero Vera, Department of Anatomical Pathology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas 35019, Spain
Cristina Bilbao-Sieyro, María Teresa Gómez-Casares, Department of Hematology, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria 35019, Las Palmas de Gran Canaria, Spain
Cristina Bilbao-Sieyro, Department of Morphology, Universitario de Las Palmas de Gran Canaria, Las Palmas 35001, Spain
María Teresa Gómez-Casares, Medical Science, Universitario de Las Palmas de Gran Canaria, Las Palmas 35001, Spain
Author contributions: Stuckey R performed the majority of the writing, and prepared the tables; Luzardo Henríquez H, de la Nuez Melian H and Rivero Vera JC provided input in writing the paper; Bilbao-Sieyro C and Gómez-Casares MT coordinated the writing of the paper; all authors approved the final version of the manuscript.
Conflict-of-interest statement: All the authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cristina Bilbao-Sieyro, PhD, Lecturer, Technician, Department of Hematology, Hospital Universitario de Gran Canaria Dr. Negrin, Barranco de la Ballena, Las Palmas de Gran Canaria 35019, Las Palmas de Gran Canaria, Spain. bilbaocristina@gmail.com
Received: December 21, 2022
Peer-review started: December 21, 2022
First decision: March 24, 2023
Revised: March 24, 2023
Accepted: April 4, 2023
Article in press: April 4, 2023
Published online: April 24, 2023
Abstract

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most common forms of aggressive and indolent lymphoma, respectively. The majority of patients are cured by standard R-CHOP immunochemotherapy, but 30%–40% of DLBCL and 20% of FL patients relapse or are refractory (R/R). DLBCL and FL are phenotypically and genetically hereterogenous B-cell neoplasms. To date, the diagnosis of DLBCL and FL has been based on morphology, immunophenotyping and cytogenetics. However, next-generation sequencing (NGS) is widening our understanding of the genetic basis of the B-cell lymphomas. In this review we will discuss how integrating the NGS-based characterization of somatic gene mutations with diagnostic or prognostic value in DLBCL and FL could help refine B-cell lymphoma classification as part of a multidisciplinary pathology work-up. We will also discuss how molecular testing can identify candidates for clinical trials with targeted therapies and help predict therapeutic outcome to currently available treatments, including chimeric antigen receptor T-cell, as well as explore the application of circulating cell-free DNA, a non-invasive method for patient monitoring. We conclude that molecular analyses can drive improvements in patient outcomes due to an increased understanding of the different pathogenic pathways affected by each DLBCL subtype and indolent FL vs R/R FL.

Keywords: Next-generation sequencing, Prognosis, Molecular analysis, Targeted therapy, Chimeric antigen receptor T-cell therapy, Personalized medicine

Core Tip: Molecular studies in the past decade have improved our understanding of the biological heterogeneity of B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Next-generation sequencing studies are helping to reveal the different pathogenic pathways affected by each DLBCL subtype and identify new targets for directed therapy. Molecular analysis can also help predict therapeutic outcome to currently available treatments, including chimeric antigen receptor T-cell therapy, and identify candidates for clinical trials with targeted therapies, ultimately leading to improvements in patient outcomes. As such, the incorporation of precision medicine via the integration of molecular analyses in clinical practice can improve clinical outcomes in patients and thus contribute to a new standard of care for patients with B-cell lymphomas.