Biological and Clinical Implications of Gene-Expression Profiling in Diffuse Large B-Cell Lymphoma: A Proposal for a Targeted BLYM-777 Consortium Panel as Part of a Multilayered Analytical Approach

Cancers, vol. 14, pp. 1857

Abstract

Gene-expression profiling (GEP) is used to study the molecular biology of lymphomas. Here, advancing insights from GEP studies in diffuse large B-cell lymphoma (DLBCL) lymphomagenesis are discussed. GEP studies elucidated subtypes based on cell-of-origin principles and profoundly changed the biological understanding of DLBCL with clinical relevance. Studies integrating GEP and next-generation DNA sequencing defined different molecular subtypes of DLBCL entities originating at specific anatomical localizations. With the emergence of high-throughput technologies, the tumor microenvironment (TME) has been recognized as a critical component in DLBCL pathogenesis. TME studies have characterized so-called "lymphoma microenvironments" and "ecotypes". Despite gained insights, unexplained chemo-refractoriness in DLBCL remains. To further elucidate the complex biology of DLBCL, we propose a novel targeted GEP consortium panel, called BLYM-777. This knowledge-based biology-driven panel includes probes for 777 genes, covering many aspects regarding B-cell lymphomagenesis (f.e., MYC signature, TME, immune surveillance and resistance to CAR T-cell therapy). Regarding lymphomagenesis, upcoming DLBCL studies need to incorporate genomic and transcriptomic approaches with proteomic methods and correlate these multi-omics data with patient characteristics of well-defined and homogeneous cohorts. This multilayered methodology potentially enhances diagnostic classification of DLBCL subtypes, prognostication, and the development of novel targeted therapeutic strategies.

Authors 18

1. Fleur A. de Groot Aachen Department of Hematology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

2. Ruben A. L. de Groen Aachen Department of Hematology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

3. Anke van den Berg

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Pathology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

4. Patty M. Jansen Aachen Department of Pathology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands

5. King Hong Lam

   Erasmus MC

   Affiliation as printed

   Department of Pathology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands

6. Pim G. N. J. Mutsaers

   Erasmus MC

   Affiliation as printed

   Department of Hematology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands

7. Carel J.M. van Noesel

   Amsterdam University Medical Centers

   Affiliation as printed

   Department of Pathology, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands

8. Martine E.D. Chamuleau

   Amsterdam University Medical Centers · Cancer Center Amsterdam

   Affiliation as printed

   Cancer Center Amsterdam and LYMMCARE, Department of Hematology, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands

9. Wendy B.C. Stevens

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Hematology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands

10. Jéssica Rodrigues Plaça

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Department of Pathology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

11. Rogier Mous

    University Medical Center Utrecht

    Affiliation as printed

    Department of Hematology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands

12. Marie José Kersten

    Amsterdam University Medical Centers · Cancer Center Amsterdam

    Affiliation as printed

    Cancer Center Amsterdam and LYMMCARE, Department of Hematology, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands

13. Marjolein van der Poel

    Maastricht University Medical Centre · Maastricht University

    Affiliation as printed

    Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands

14. Thomas Tousseyn

    Universitair Ziekenhuis Leuven

    Affiliation as printed

    Department of Pathology, University Hospitals Leuven, 3000 Leuven, Belgium

15. Feng Jung Sherida H. Woei-A-Jin

    Universitair Ziekenhuis Leuven

    Affiliation as printed

    Department of General Medical Oncology, University Hospitals Leuven, 3000 Leuven, Belgium

16. Arjan Diepstra

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Department of Pathology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

17. Marcel Nijland

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Department of Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

18. Joost S.P. Vermaat corresponding Aachen Department of Hematology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands