Journal Article

Editorial: Mouse Models of B Cell Malignancies

Vincent-Fabert, Christelle, Perez-Chacon, Gema, Zapata, Juan M.

2021

Overview

Furthermore, the next generation sequencing has opened new possibilities for forward and reverse genetic screenings to identify gene mutations involved in tumor development, progression, evasion and relapse, both in human and mice, shaping the field for an exciting future. A mutation in the MyD88 gene introducing a leucine in position 265 instead of a proline causing constitutive MyD88 dimerization and NFKB and JAK activation is found in a variety of human B cell neoplasms (2), including in most patients with WM (3).Schmidt et al.developed three genetically engineered conditional mouse models harboring floxed-Myd88L252P (the mouse homolog of the human L265P mutation), one with Cre under the control of CD19 (CD19-Cre mice), where Myd88L252P expression is enforced in all B cells, a second mouse strain with Cre under the control of Cγ1 promoter (Cγ1-Cre mice), thus limiting Myd88L252P expression to GC cell, and a third mouse line with restricted MyD88L252P expression to a few random B cells (CD19-CreERT2 mice). Dysregulation of c-MYC is a trademark of a variety of B-cell lymphomas, where translocations of this gene lead to overexpression of intact c-MYC protein (8). c-MYC translocation is a primary transformation event in Burkitt´s lymphoma but its occurrence as a secondary event in diffuse large B-cell lymphoma, plasmablastic lymphoma, mantle cell lymphoma, or double-hit lymphoma fuels the aggressiveness of these lymphomas.Ferrad et al.overview the various c-Myc-driven mouse models of lymphoma focusing on those mouse models of c-myc overexpression regulated by the two main enhancers in the Igh locus, namely, Eµ and 3´RR enhancer. In addition,Malaney et al.also overview the various transgenic mouse models of B cell lymphoma based on c-MYC upregulation, with particular emphasis on the heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a driver of B cell lymphoma through its role on c-Myc regulation. hnRNP K is a ssDNA and RNA binding protein that regulates a plethora of processes controlling transcription and translation (9) and its over- and under-expression is causative of cancer (10). hnRNP K has been shown to be upregulated in DLBCL and Burkitt´s lymphoma patients and the oncogenic role of hnRNP K was previously confirmed by the authors by means of a B cell specific Eµ-hnRNP K transgenic mice that develop B cell lymphomas with high latency and high incidence (11). hnRNP K’s oncogenic potential stems from its ability to regulate c-MYC expression at post-transcriptional and translational level, without requiring c-MYC translocations.

• Publisher: Frontiers Media SA,Frontiers,Frontiers Media S.A
• Subject: Adaptive immunology / Animal models / Animals / Apoptosis / B cell neoplasms / B-cell lymphoma / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / c-Myc protein / Cancer / CD19 antigen / Cell culture / Dimerization / Enhancers / Epigenetics / GEMM / Gene Expression Regulation, Neoplastic / Genes / Genetic engineering / Genetic screening / Genetic transformation / genetically engineered mouse models / Heavy chains / Hematology / Human health and pathology / Immunoglobulins / Immunology / immunosurveillance / Latency / Leukemia / Leukemia, B-Cell - genetics / Leukemia, B-Cell - immunology / Leukemia, B-Cell - metabolism / Leukemia, B-Cell - pathology / Life Sciences / Lymphocytes B / Lymphoma / Lymphoma, B-Cell - genetics / Lymphoma, B-Cell - immunology / Lymphoma, B-Cell - metabolism / Lymphoma, B-Cell - pathology / Malignancy / Mantle cell lymphoma / Medical prognosis / Mice, Transgenic / Mitochondria / mouse leukemia / mouse lymphoma / Mutagenesis / Mutation / Myc protein / MyD88 protein / Next-generation sequencing / NF-κB protein / Plasma / Point mutation / Post-transcription / Protein transport / RNA-binding protein / Signal Transduction / Transgenic animals / Transgenic mice / Tumor Escape / Tumors