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Myelodysplastische Syndrome

Epidemiologie, molekulare und morphologische Merkmale, Risikostratifizierung

Myelodysplastic syndromes

Epidemiology, molecular and morphological characteristics and risk stratification

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Zusammenfassung

Myelodysplastische Syndrome (MDS) umfassen ein Spektrum klonaler hämatopoetischer Stammzellerkrankungen, die nach den Kriterien der 2008 revidierten Klassifikation der WHO eingeordnet werden. Eine Weiterentwicklung ist zu erwarten. Das klinische Krankheitsbild ist durch ungeklärte periphere Zytopenien gekennzeichnet, die zu Anämie, Blutungsereignissen und vermehrter Infektanfälligkeit führen. Das meist hyper-, selten hypozelluläre, gelegentlich auch fibrosierte Knochenmark zeigt Dysplasien in ≥ 10% der Zellen zumindest einer oder aber mehrerer hämatopoetischer Zellreihen. Diese Veränderungen sowie eine gesteigerte Apoptoserate, Stammzellseneszenz und eine immunologische Dysregulation führen zu einer ineffektiven Hämatopoese. Die diagnostische Aufarbeitung sollte komplementäre hämatologische, morphologische und zytogenetische/molekulare Parameter berücksichtigen. Das Methodenspektrum umfasst zytologische Untersuchungen von Blut und Knochenmark, Zytogenetik, Fluoreszenz-in-situ-Hybridisierung (FISH), Beckenkammtrepanate, Immunphänotypisierung und Evaluation molekularer Marker durch etablierte und neue Techniken. Mutationen, die Wachstumsfaktorrezeptoren, Regulatoren von Zellzyklus und Apoptose, intrazelluläre Signalwege, Transkriptionsfaktoren, epigenetische Regulationsmechanismen und das Splicosom betreffen, sind an der MDS-Pathogenese und -Progression beteiligt.

Abstract

Myelodysplastic syndromes (MDS) comprise a spectrum of clonal stem cell disorders which are currently defined according to the classification scheme of the revised 2008 WHO classification but which may be further refined in the future. The clinical presentation is often characterized by unexplained isolated or multiple peripheral blood cytopenias resulting in anemia, bleeding events or increased susceptibility to infections. The generally hypercellular, but rarely hypocellular and occasionally fibrotic bone marrow shows dysplastic features in ≥ 10 % of cells of at least one of the hematopoietic lineages. These features and enhanced apoptosis, stem cell senescence and immunologic dysregulation result in ineffective hematopoiesis. Diagnostics in MDS relies on complementary consideration of hematological, morphological and cytogenetic/molecular parameters. Methods include marrow and peripheral blood cytology, cytogenetics, fluorescence in situ hybridization (FISH), trephine bone marrow biopsy examination, immunophenotyping and the evaluation of molecular markers by established and new techniques. Mutations affecting growth factor receptors, cell cycle and apoptosis regulators, intracellular signaling, transcription factors, epigenetic regulation and the splicosome are involved in MDS pathogenesis and progression.

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Authors and Affiliations

  1. Institut für Pathologie, Universitätsklinikum Freiburg, Breisacherstr. 115a, 79106, Freiburg, Deutschland

    A.H. Schmitt-Graeff & P. Fisch

  2. Medizinische Klinik 1, Universitätsklinikum Freiburg, Hugstetterstr. 55, 79106, Freiburg, Deutschland

    M.J. Müller

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  1. A.H. Schmitt-Graeff
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Correspondence to A.H. Schmitt-Graeff.

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Schmitt-Graeff, A., Müller, M. & Fisch, P. Myelodysplastische Syndrome. Pathologe 34, 45–55 (2013). https://doi.org/10.1007/s00292-012-1707-4

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