A Novel Megakaryocyte Subpopulation Poised to Exert the Function of HSC Niche as Possible Driver of Myelofibrosis

Careful morphological investigations, coupled with experimental hematology studies in animal models and in in vitro human cultures, have identified that platelets are released in the circulation by mature megakaryocytes generated by hematopoietic stem cells by giving rise to lineage-restricted progenitor cells and then to morphologically recognizable megakaryocyte precursors, which undergo a process of terminal maturation. Advances in single cell profilings are revolutionizing the process of megakaryocytopoiesis as we have known it up to now. They identify that, in addition to megakaryocytes responsible for producing platelets, hematopoietic stem cells may generate megakaryocytes, which exert either immune functions in the lung or niche functions in organs that undergo tissue repair. Furthermore, it has been discovered that, in addition to hematopoietic stem cells, during ontogeny, and possibly in adult life, megakaryocytes may be generated by a subclass of specialized endothelial precursors. These concepts shed new light on the etiology of myelofibrosis, the most severe of the Philadelphia negative myeloproliferative neoplasms, and possibly other disorders. This perspective will summarize these novel concepts in thrombopoiesis and discuss how they provide a framework to reconciliate some of the puzzling data published so far on the etiology of myelofibrosis and their implications for the therapy of this disease.

48th Congress of the Italian Society of Hematology - 16th Congress of the Italian Society of Experimental Hematology

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ДОСЯГНЕННЯ ДОСЛІДЖЕННЯ ЕКСТРАМЕДУЛЯРНОГО ГЕМАТОПОЕЗУ В СЕЛЕЗІНЦІ

Thanks to the researches by William Houston, Magnus Falconar, Julian Evans we know that the spleen has powerful immune protection, is able to synthesize humoral immunity factors, it is the organ of detoxification, re-mobilization of iron, and it is involved in hemopoiesis. However, among all of functions, the hemopoietic function of the spleen still not fully explored. This is due to the fact that the extemedular hematopoiesis (EMH) is considered by most scientists as a manifestation of the pathological condition related to the failure of the bone marrow function, because physiologically, it completely stops after the embryonic development period and is almost uncharacteristic for the post-embryonic period. This process involves the production of mature blood cells outside the medullary bone cavity. EMH is often observed in patients with myelofibrosis, myeloproliferative disorders and hemoglobinopathy, especially with thalassemia and sickle cell anemia. The key organs of peripheral hematopoiesis that participate in EMH are spleen, liver and lymph nodes.Today there are not enough researches on the fundamental processes and the very mechanism of EMH. The article presents an analysis of modern EMH researches based on publications on experimental hematology. During the analysis, prospective directions for further research were identified.