Abstract 4634: Mouse model for nodal marginal zone lymphoma

Abstract

Introduction: Indolent B-Cell Non-Hodgkin’s Lymphoma (i-NHL) represents a heterogeneous group of lymphoproliferative malignancies, encompassing 40% of NHL, that remains largely incurable. The B-cell receptor signaling pathway is activated in B-cell malignancy and mediates its activity mainly through the Phosphoinositide 3-kinase (PI3K) pathway. Furthermore, novel PI3K inhibitors, such as idelalisib and copanlisib, have shown impressive clinical activity in several indolent lymphomas including marginal zone lymphoma (MZL). This further supports the important role of the PI3K pathway in these tumors. Methods We generated a genetically engineered mouse model carrying heterozygous knockout alleles of both the tumor suppressor genes Phosphatase and Tensin Homolog (PTEN) and Liver Kinase B1 (LKB1), leading to over-activation of the PI3K-mTOR pathway in all mouse tissues. We closely monitored these mice for tumor formation by at least weekly physical examinations for several months. Upon tumor detection, tumor size was recorded weekly using calipers, with an experimental endpoint of 15-20mm in any dimension. One half of the tumor was immediately preserved in a 4% paraformaldehyde solution and prepared for sectioning, HE 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4634.