AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

• DOI: 10.1172/jci.insight.90036
• Publication Date: 2017-07-05T15:26:07Z
• Authors: V. Lokesh Battula; Phuong M. Le; Jeffrey C. Sun; Khoa Nguyen; Bin Yuan; Ximin Zhou; Sonali Sonnylal; Teresa McQueen; Vivian Ruvolo; Keith A. Michel; Xiaoyang Ling; Rodrigo Jacamo; Elizabeth Shpall; Zhiqiang Wang; Arvind Rao; Gheath Al-Atrash; Marina Konopleva; R. Eric Davis; Melvyn A. Harrington; Catherine W. Cahill; Carlos Bueso-Ramos; Michael Andreeff
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, particular osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter BM microenvironment create a hospitable niche. Here, we report that acute myeloid (AML) but not normal CD34+ or CD33+ induce osteogenic differentiation mesenchymal stromal (MSCs). In addition, AML inhibited adipogenic of MSCs. Mechanistic studies identified AML-derived BMPs activate Smad1/5 signaling Gene expression array analysis revealed connective tissue growth factor (CTGF) BM-MSCs irrespective type. Overexpression CTGF transgenic mouse model greatly enhanced engraftment vivo. Together, our data suggest preosteoblast-rich niche turn enhances expansion.