Abstract 3292: Manipulating osteoblast differentiation in order to inhibit protection of AML cells within the bone marrow

Abstract

Abstract While standard chemotherapeutics can initially induce remission in patients with acute myelogenous leukemia (AML), patients often relapse in part due to the protective bone marrow microenvironment, which promotes the survival of AML cells. Using an in vitro cell culture model of the bone marrow, our lab recently showed that differentiating osteoblasts potently protect AML cells from apoptosis. In addition, we found that differentiating osteoblasts treated with histone deacetylase inhibitors (HDACi) fail to protect AML cells in this model. Since HDACi decreased the expression of genes required for osteoblast differentiation, we hypothesize that blocking specific stage(s) of osteoblast differentiation may make AML cells within the bone marrow more susceptible to chemotherapy. We are currently disrupting specific osteoblast differentiation stages via molecular or therapeutic drug manipulation and exploring the impact on AML cell survival both in cell culture models of the bone marrow microenvironment and in a mouse model of AML. The results of our studies will characterize novel bone marrow molecular and cellular interactions that promote the survival of AML cells. Targeting these interactions in combination therapies may more completely eradicate the AML cell reservoir and better prevent relapse. Citation Format: Rosalie Sterner, Kimberly Kremer, Amel Dudakovic, Scott Kaufmann, Jennifer Westendorf, Andre van Wijnen, Karen Hedin. Manipulating osteoblast differentiation in order to inhibit protection of AML cells within the bone marrow. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3292.