Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support

• Published in: Leukemia 2020-02, Vol.34 (2), p.391-403
• Main Authors: Azadniv, Mitra, Myers, Jason R., McMurray, Helene R., Guo, Naxin, Rock, Phil, Coppage, Myra L., Ashton, John, Becker, Michael W., Calvi, Laura M., Liesveld, Jane L.
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/2; 13/31; 631/67/327; 692/699/67/1990/283/1897; Acute myeloid leukemia; Adipogenesis; Adipogenesis - physiology; Aged; Aged, 80 and over; Analysis; Bone marrow; Bone Marrow - metabolism; Bone Marrow - pathology; Bone Marrow Cells - metabolism; Bone Marrow Cells - pathology; Cancer Research; Cell differentiation; Cell Differentiation - physiology; Cell Line, Tumor; Cell proliferation; Cell Proliferation - physiology; Cell survival; Critical Care Medicine; Cytotoxicity; Depletion; Egr-2 protein; Female; Hematology; Hematopoietic stem cells; Humans; In vivo methods and tests; Intensive; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Male; Medicine; Medicine & Public Health; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Mesenchyme; Middle Aged; Myeloid leukemia; Oncology; Progenitor cells; Ribonucleic acid; RNA; RNA sequencing; Sox9 protein; SOX9 Transcription Factor - metabolism; Stem cells; Stromal cells; Survival
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-019-0568-8

Bone marrow mesenchymal stromal cells (MSCs) constitute one of the important components of the hematopoietic microenvironmental niche. In vivo studies have shown that depletion of marrow MSCs resulted in reduction of hematopoietic stem cell content, and there is in vitro evidence that marrow MSCs are able to support leukemia progenitor cell proliferation and survival and provide resistance to cytotoxic therapies. How MSCs from leukemia marrow differ from normal counterparts and how they are influenced by the presence of leukemia stem and progenitor cells are still incompletely understood. In this work, we compared normal donor (ND) and acute myelogenous leukemia (AML) derived MSCs and found that AML-MSCs had increased adipogenic potential with improved ability to support survival of leukemia progenitor cells. To identify underlying changes, RNA-Seq analysis was performed. Gene ontology and pathway analysis revealed adipogenesis to be among the set of altered biological pathways dysregulated in AML-MSCs as compared with ND-MSCs. Expression of both SOX9 and EGR2 was decreased in AML-MSCs as compared with ND-MSCs. Increasing expression of SOX9 decreased adipogenic potential of AML-MSCs and decreased their ability to support AML progenitor cells. These findings suggest that AML-MSCs possess adipogenic potential which may enhance support of leukemia progenitor cells.