Conditional expression of HGAL leads to the development of diffuse large B-cell lymphoma in mice

Content Provider	Scilit
Author	Raboso-Gallego, Javier Casado-García, Ana Jiang, Xiaoyu Isidro-Hernández, Marta Gentles, Andrew J. Zhao, Shuchun Natkunam, Yasodha Blanco, Oscar Domínguez, Verónica Pintado, Belén Alonso-López, Diego Rivas, Javier De Las Vicente-Dueñas, Carolina Lossos, Izidore S. Sanchez-Garcia, Isidro
Copyright Year	2021
Description	Diffuse large B-cell lymphomas (DLBCLs) are clinically and genetically heterogeneous tumors. Deregulation of diverse biological processes specific to B cells, such as B-cell receptor (BCR) signaling and motility regulation, contribute to lymphomagenesis. Human germinal center associated lymphoma (HGAL) is a B-cell–specific adaptor protein controlling BCR signaling and B lymphocyte motility. In normal B cells, it is expressed in germinal center (GC) B lymphocytes and promptly downregulated upon further differentiation. The majority of DLBCL tumors, primarily GC B-cell types, but also activated types, express HGAL. To investigate the consequences of constitutive expression of HGAL in vivo, we generated mice that conditionally express human HGAL at different stages of hematopoietic development using 3 restricted Cre-mediated approaches to initiate expression of HGAL in hematopoietic stem cells, pro-B cells, or GC B cells. Following immune stimulation, we observed larger GCs in mice in which HGAL expression was initiated in GC B cells. All 3 mouse strains developed DLBCL at a frequency of 12% to 30% starting at age 13 months, leading to shorter survival. Immunohistochemical studies showed that all analyzed tumors were of the GC B-cell type. Exon sequencing revealed mutations reported in human DLBCL. Our data demonstrate that constitutive enforced expression of HGAL leads to DLBCL development.
Related Links	https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2020004996/1760805/blood.2020004996.pdf
Ending Page	1753
Page Count	13
Starting Page	1741
DOI	10.1182/blood.2020004996
Journal	Blood
Issue Number	13
Volume Number	137
Language	English
Publisher	American Society of Hematology
Publisher Date	2021-04-01
Access Restriction	Open
Subject Keyword	Hematology Research and Experimental Medicine Hematopoietic Diverse Dlbcl Lymphoma Expression of Hgal Protein Survival Differentiation Journal: Blood (Vol- 123, Issue- 13)
Content Type	Text
Resource Type	Article