Megakaryopoiesis is a complex, stepwise process that takes place largely in the bone marrow. At the apex of the hierarchy, hematopoietic stem cells undergo a number of lineage commitment decisions that ultimately lead to the production of polyploid megakaryocytes. On average, megakaryocytes release 1011 platelets per day into the blood that repair vascular injuries and prevent excessive bleeding. This differentiation process is tightly controlled by exogenous and endogenous factors, which have been the topics of intense research in the hematopoietic field. Indeed, a skewing of megakaryocyte commitment and differentiation may entail the onset of myeloproliferative neoplasms and other preleukemic disorders together with acute megakaryoblastic leukemia, whereas quantitative or qualitative defects in platelet production can lead to inherited platelet disorders. The recent advent of next-generation sequencing has prompted mapping of the genomic landscape of these conditions to provide an accurateview of the underlying lesions. The aims of this review are to introduce the physiological pathways of megakaryopoiesis and to present landmark studies on acquired and inherited disorders that target them. These studies have not only introduced a new era in the fields of molecular medicine and targeted therapies but may also provide us with a better understanding ofthemechanismsunderlying normalmegakaryopoiesis and thrombopoiesis that can informeffortsto create alternativesources of megakaryocytes and platelets.
|Data di pubblicazione:||2016|
|Titolo:||Genomic landscape of megakaryopoiesis and platelet function defects|
|Autori:||Bianchi, Elisa; Norfo, Ruggiero; Pennucci, Valentina; Zini, Roberta; Manfredini, Rossella|
|Digital Object Identifier (DOI):||10.1182/blood-2015-07-607952|
|Appare nelle tipologie:||Articolo su rivista|
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