title: Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis-Masters of Survival and Clonality?
abstract: Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the "reprogramming" of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs.
authors.affiliation: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria. l.pleyer@salk.at.|Center for Clinical Cancer and Immunology Trials at Salzburg Cancer Research Institute, 5020 Salzburg, Austria. l.pleyer@salk.at.|3rd Medical Department, Cancer Cluster Salzburg, 5020 Salzburg, Austria. l.pleyer@salk.at.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pleyer
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology &amp; Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, 1090 Vienna, Austria. peter.valent@meduniwien.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: 3rd Medical Department with Hematology and Medical Oncology, Hemostaseology, Rheumatology and Infectious Diseases, Laboratory for Immunological and Molecular Cancer Research, Oncologic Center, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria. r.greil@salk.at.|Center for Clinical Cancer and Immunology Trials at Salzburg Cancer Research Institute, 5020 Salzburg, Austria. r.greil@salk.at.|3rd Medical Department, Cancer Cluster Salzburg, 5020 Salzburg, Austria. r.greil@salk.at.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D055153:Stem Cell Niche
keywords: acute myeloid leukemia (AML); bone marrow stem cell niche; endothelial-to-mesenchymal transition; epithelial-to-mesenchymal transition; immunomodulation; leukemic niche; mesenchymal stem cells (MSC); microenvironment; myelodysplastic syndromes (MDS); neoplastic stem cells