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

Venkata 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. CahillCarlos Bueso-Ramos, Michael Andreeff

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

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

Original languageEnglish (US)
Article numbere90036
JournalJCI Insight
Volume2
Issue number13
DOIs
StatePublished - Jul 6 2017

Keywords

  • Bone Biology
  • Stem cells

ASJC Scopus subject areas

  • General Medicine

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource
  • Flow Cytometry and Cellular Imaging Facility
  • Research Animal Support Facility
  • Small Animal Imaging Facility

Fingerprint

Dive into the research topics of 'AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth'. Together they form a unique fingerprint.

Cite this