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Lue et al. J Cancer Metastasis Treat 2022;8:11 Journal of Cancer
DOI: 10.20517/2394-4722.2021.193
Metastasis and Treatment

Review Open Access

Diffuse large B-Cell lymphoma: from novel
molecular classifications to tailored targeted

therapies

1
Jennifer K. Lue , Grzegorz S. Nowakowski 2
1
Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, United States
2
Department of Medicine, Mayo Clinic, Rochester, Minnesota, MN 55902, United States
Correspondence to: Dr. Jennifer K. Lue, Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center,
530 East 74th Street, New York, NY 10021, USA. E-mail: luej@mskcc.org

How to cite this article: Lue JK, Nowakowski GS. Diffuse large B-Cell lymphoma: from novel molecular classifications to tailored
targeted therapies. J Cancer Metastasis Treat 2022;8:11. https://dx.doi.org/10.20517/2394-4722.2021.193

Received: 12 Oct 2021 First Decision: 8 Nov 2021 Revised: 24 Jan 2022 Accepted: 10 Mar 2022 Published: 31 Mar 2022

Academic Editor: Owen A. O’Connor, Lucio Miele Copy Editor: Jia-Xin Zhang Production Editor: Jia-Xin Zhang

Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease comprising multiple genetic subtypes that
translates and impacts clinical outcomes after standard chemoimmunotherapy. Our initial understanding of the
complex biological subtypes of DLBCL began with the identification of cell of origin (COO), and now has evolved to
include even more specific subtypes defined by genetic signatures and mutations. These newer classifications lend
themselves to the application of precision-based medicine, allowing us to tailor new treatment platforms that
target specific oncogenic drivers in order to improve DLBCL outcomes. Essential to this is the development of
genetic assays and tools that are reliable and readily available to assist in the application of these molecular
classifications to real-world use. In this review, we discuss the history of DLBCL classification systems and their
implication on clinical investigation as well as novel therapeutic options in DLBCL.

Keywords: DLBCL, tumor heterogeneity, activated-B-cell, germinal center, molecular targets

INTRODUCTION
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) and is
characterized by highly diverse molecular subtypes. Gene expression profiling (GEP) has delineated two

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
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