tailieunhanh - Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases (Part 9)

Etiology Megakaryocytopoiesis and platelet production depend upon thrombopoietin and its receptor, Mpl. As in the case of early erythroid and myeloid progenitor cells, early megakaryocytic progenitors require the presence of interleukin 3 (IL-3) and stem cell factor for optimal proliferation in addition to thrombopoietin. Their subsequent development is also enhanced by the chemokine stromal cell–derived factor 1 (SDF-1). However, megakaryocyte maturation and differentiation require thrombopoietin. Megakaryocytes are unique among hematopoietic progenitor cells because reduplication of their genome is endomitotic rather than mitotic. In the absence of thrombopoietin, endomitotic megakaryocytic reduplication and, by extension, the cytoplasmic development necessary for platelet production are. | Chapter 103. Polycythemia Vera and Other Myeloproliferative Diseases Part 9 Etiology Megakaryocytopoiesis and platelet production depend upon thrombopoietin and its receptor Mpl. As in the case of early erythroid and myeloid progenitor cells early megakaryocytic progenitors require the presence of interleukin 3 IL-3 and stem cell factor for optimal proliferation in addition to thrombopoietin. Their subsequent development is also enhanced by the chemokine stromal cell-derived factor 1 SDF-1 . However megakaryocyte maturation and differentiation require thrombopoietin. Megakaryocytes are unique among hematopoietic progenitor cells because reduplication of their genome is endomitotic rather than mitotic. In the absence of thrombopoietin endomitotic megakaryocytic reduplication and by extension the cytoplasmic development necessary for platelet production are impaired. Like erythropoietin thrombopoietin is produced in both the liver and the kidneys and an inverse correlation exists between the platelet count and plasma thrombopoietic activity. Like erythropoietin plasma levels of thrombopoietin are controlled largely by the size of its progenitor cell pool. In contrast to erythropoietin but like its myeloid counterparts granulocyte- and granulocyte-macrophage colonystimulating factors thrombopoietin not only enhances the proliferation of its target cells but also enhances the reactivity of their end-stage product the platelet. In addition to its role in thrombopoiesis thrombopoietin also enhances the survival of multipotent hematopoietic stem cells. The clonal nature of ET was established by analysis of glucose-6-phosphate dehydrogenase isoenzyme expression in patients hemizygous for this gene by analysis of X-linked DNA polymorphisms in informative women patients and by the expression in patients of nonrandom though variable cytogenetic abnormalities. Although thrombocytosis is its principal manifestation like the other chronic myeloproliferative disorders a .