Myelodysplasia is in the niche: novel concepts and emerging therapies.
Myelodysplastic syndromes (MDSs) represent clonal disorders mainly of the elderly that are characterized by ineffective hematopoiesis and an increased risk of transformation into acute myeloid leukemia. The pathogenesis of MDS is thought to evolve from accumulation and selection of specific genetic or epigenetic events. Emerging evidence indicates that MDS is not solely a hematopoietic disease but rather affects the entire bone marrow microenvironment, including bone metabolism. Many of these cells, in particular mesenchymal stem and progenitor cells (MSPCs) and osteoblasts, express a number of adhesion molecules and secreted factors that regulate blood regeneration throughout life by contributing to hematopoietic stem and progenitor cell (HSPC) maintenance, self-renewal and differentiation. Several endocrine factors, such as erythropoietin, parathyroid hormone and estrogens, as well as deranged iron metabolism modulate these processes. Thus, interactions between MSPC and HSPC contribute to the pathogenesis of MDS and associated pathologies. A detailed understanding of these mechanisms may help to define novel targets for diagnosis and possibly therapy. In this review, we will discuss the scientific rationale of 'osteohematology' as an emerging research field in MDS and outline clinical implications.
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl-Gustav-Carus, Technische Universität, Dresden, Germany.
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Bulycheva
Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl-Gustav-Carus, Technische Universität, Dresden, Germany.
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Rauner
Georg-Speyer-Haus, Institut for Tumor Biology and Experimental Therapy, 60596, Frankfurt am Main, Germany.
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Medyouf
Department of Internal Medicine VI, Medical University of Innsbruck, Innsbruck, Austria.
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Theurl
1] Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl-Gustav-Carus, Technische Universität, Dresden, Germany [2] Center for Regenerative Therapies Dresden, Technical University, Dresden, Germany.
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Bornhäuser
1] Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl-Gustav-Carus, Technische Universität, Dresden, Germany [2] Center for Regenerative Therapies Dresden, Technical University, Dresden, Germany.
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Hofbauer
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl-Gustav-Carus, Technische Universität, Dresden, Germany.
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Platzbecker
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D044127:Epigenesis, Genetic; D004921:Erythropoietin / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007501:Iron / Q000737:chemistry; D019190:Iron Overload / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000473:pathology*; D010006:Osteoblasts / Q000166:cytology; D010281:Parathyroid Hormone / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D010281:Parathyroid Hormone; D004921:Erythropoietin; D007501:Iron