title: Mesenchymal stromal cells in myeloid malignancies.
abstract: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis. Additionally, it was demonstrated as a 'proof of principle' that genetic disruption of cells of the mesenchymal or osteoblastic lineage can induce MDS, MPS or AML in mice. In this review, we summarize the current knowledge about the contribution of the BM microenvironment, in particular mesenchymal stromal cells (MSC) to the pathogenesis of AML and MDS. Furthermore, potential models integrating the BM microenvironment into the pathophysiology of these myeloid disorders are discussed. Finally, strategies to therapeutically exploit this knowledge and to interfere with the crosstalk between clonal hematopoietic cells and altered stem cell niches are introduced.
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Düesseldorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schroeder
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Düesseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Geyh
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Düesseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Medical Faculty, Düesseldorf, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
keywords: Acute myeloid leukemia; Hematopoiesis; Mesenchymal stromal cells; Myelodysplastic syndromes; Niche