Clinical and Biological Subtypes of B-cell Lymphoma Revealed by Microenvironmental Signatures
Top Cited Papers
Open Access
- 4 February 2021
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Discovery
- Vol. 11 (6), 1468-1489
- https://doi.org/10.1158/2159-8290.cd-20-0839
Abstract
Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease. Transcriptomic and genetic characterization of DLBCL has increased the understanding of its intrinsic pathogenesis and provided potential therapeutic targets. However, the role of the microenvironment in DLBCL biology remains less understood. Here, we performed a transcriptomic analysis of the microenvironment of 4,655 DLBCLs from multiple independent cohorts and described four major lymphoma microenvironment categories that associate with distinct biological aberrations and clinical behavior. We also found evidence of genetic and epigenetic mechanisms deployed by cancer cells to evade microenvironmental constraints of lymphoma growth, supporting the rationale for implementing DNA hypomethylating agents in selected patients with DLBCL. In addition, our work uncovered new therapeutic vulnerabilities in the biochemical composition of the extracellular matrix that were exploited to decrease DLBCL proliferation in preclinical models. This novel classification provides a road map for the biological characterization and therapeutic exploitation of the DLBCL microenvironment. In a translational relevant transcriptomic-based classification, we characterized the microenvironment as a critical component of the B-cell lymphoma biology and associated it with the DLBCL clinical behavior establishing a novel opportunity for targeting therapies. This article is highlighted in the In This Issue feature, p. 1307Keywords
Other Versions
Funding Information
- Leukemia and Lymphoma Society (LLS-SCOR 7012-16, LLS TRP R6510-19)
- NIH NCI (R01CA242069)
This publication has 84 references indexed in Scilit:
- GSVA: gene set variation analysis for microarray and RNA-Seq dataBMC Bioinformatics, 2013
- NCBI GEO: archive for functional genomics data sets—updateNucleic Acids Research, 2012
- DELLY: structural variant discovery by integrated paired-end and split-read analysisBioinformatics, 2012
- Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activationBlood, 2012
- Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomesNature Medicine, 2011
- Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applicationsBioinformatics, 2011
- The Sequence Read ArchiveNucleic Acids Research, 2010
- BEDTools: a flexible suite of utilities for comparing genomic featuresBioinformatics, 2010
- Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survivalBlood, 2009
- Germinal-Center Organization and Cellular DynamicsImmunity, 2007