Work

Tumor Trp53 status and genotype affect the bone marrow microenvironment in acute myeloid leukemia

Year: 2017

Type: article

Abstract: // Rodrigo Jacamo 1 , R. Eric Davis 2 , Xiaoyang Ling 3 , Sonali Sonnylal 1 , Zhiqiang Wang 2 , Wencai Ma 2 , Min Zhang 2 , Peter Ruvolo 1 , Vivian Ruvolo 1 , Rui-Yu Wang 1 , Teresa McQueen 1 , Scott Lowe 4 , Johannes Zuber 5 , Steven M. Kornblau 1 , Marina Konopleva 1 and Michael Andreeff 1 1 Department of Leukemia, Section of Molecular Hematology and Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA 5 Research Institute of Molecular Pathology, Vienna, Austria Correspondence to: Michael Andreeff, email: // Keywords : AML, microenvironment, GEP, stroma, genotype Received : September 23, 2016 Accepted : June 03, 2017 Published : July 06, 2017 Abstract The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds. We identified a set of genes whose expression in BM-MSC was modulated by all four AML genotypes tested. In addition, there were sets of differentially-expressed genes in AML-exposed BM-MSC that were unique to the particular AML genotype or Trp53 status. Our findings support the hypothesis that leukemia cells alter the transcriptome of surrounding BM stromal cells, in both common and genotype-specific ways. These changes are likely to be advantageous to AML cells, affecting disease progression and response to chemotherapy, and suggest opportunities for stroma-targeting therapy, including those based on AML genotype.

Source: Oncotarget

DOI: 10.18632/oncotarget.19042