An Overview on Diffuse Large B-Cell Lymphoma Models: Towards a Functional Genomics Approach

Abstract

Lymphoma research is a paradigm of the integration of basic and clinical research within the fields of diagnosis and therapy. Clinical, phenotypic, and genetic data are currently used to predict which patients could benefit from standard treatment. However, alternative therapies for patients at higher risk from refractoriness or relapse are usually empirically proposed, based on trial and error, without considering the genetic complexity of aggressive B-cell lymphomas. This is primarily due to the intricate mosaic of genetic and epigenetic alterations in lymphomas, which are an obstacle to the prediction of which drug will work for any given patient. Matching a patient’s genes to drug sensitivity by directly testing live tissues comprises the “precision medicine” concept. However, in the case of lymphomas, this concept should be expanded beyond genomics, eventually providing better treatment options for patients in need of alternative therapeutic approaches. We provide an overview of the most recent findings in diffuse large B-cell lymphomas genomics, from the classic functional models used to study tumor biology and the response to experimental treatments using cell lines and mouse models, to the most recent approaches with spheroid/organoid models. We also discuss their potential relevance and applicability to daily clinical practice.

Mouse models of diffuse large B cell lymphoma

“…The relatively low-cost and usability of CDX models make them attractive preclinical tools, however they typically do not fully recapitulate the disease complexity ( 134 ). CDX models are often cultured 2D over many passages in serum-containing media and implanted into immuno-compromised mice, such as NOD-SCID or Nude mice for drug efficacy studies ( 135 ). With the immune system as a crucial component of the antitumor response, and as immune-checkpoint-inhibitors (ICIs) are emerging as the standard of care for several cancer indications, this type of immuno-deficient mouse model system is not ideal for representing human biology ( 136 ).…”

Clinically relevant core genes for hematologic malignancies in clinical NGS panel testing

“…These findings improve our understanding of the genetic underpinnings of DLBCL, which is a critical advancement in this field. The genes associated with lymphoma and chronic lymphocytic leukemia, along with their clinical significance encompassing diagnostic, prognostic, and therapeutic impacts, are compiled and presented in Letters to the Editor Table 3 [3,7,[14][15][16][17][18][19][20] with corresponding references.…”

Expression and Clinical Significance of Ki-67, CD10, BCL6, MUM1, c-MYC, and EBV in Diffuse Large B Cell Lymphoma Patients

“…3 GCB DLBCL originates from B cells that have undergone germinal center reactions and typically have a better prognosis, whereas ABC DLBCL arises from B cells that have bypassed or failed to complete the germinal center reaction and often have a worse prognosis. 4 Since then, several studies have been consistent with Hans' prognostic division, while others have found no statistically significant differences between these 2 categories. 5,6 In addition, it has been examined that a high proliferation rate, as indicated by increased expression from the marker of proliferation Ki-67 (MKI67 or Ki-67) expression, is associated with poor prognosis and may be greater in the non-GCB subgroup.…”