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Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition

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Title: Targeting B Cell Acute Lymphoblastic Leukemia with Oncolytic Virotherapy and Histone Deacetylase Inhibition
Author: Ternamian, Christian
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Bridle, Byram W.
Abstract: B-cell acute lymphoblastic leukemia (B-ALL) is a hematological disease characterized by the proliferation and extramedullary distribution of malignant B lymphoblasts. Though conventional treatment can be relatively efficacious in pediatric B-ALL, adult B-ALL is frequently refractory to therapy. Oncolytic viruses (OVs) are novel anticancer agents that can selectively destroy tumor cells, while sparing healthy cells. Histone deacetylase inhibitors (HDIs) have antileukemic properties and can improve viral oncolysis in tumor cells. Here, we demonstrate that Maraba virus MG1 is a more potent oncolytic than vesicular stomatitis virus ∆M51 in L1210 (murine B-ALL) cells. Furthermore, Maraba virus MG1 potently synergized with HDIs in L1210 cells. Interestingly, MS-275 or SAHA in combination with the viral mimic imiquimod additively reduced L1210 cell viability. Hence, we hypothesize that OVs may sensitize B-ALL cells to HDI-mediated toxicity. In vivo, MG1 in combination with SAHA and MS-275 appeared to enhance survival in certain mice and merit further investigation.
URI: http://hdl.handle.net/10214/8293
Date: 2014-08
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