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Effects of vascular endothelial growth factors and their receptors on megakaryocytes and platelets and related diseases

Summary It is well known that vascular endothelial growth factors (VEGFs) and their receptors (vascular endothelial growth factor receptors, VEGFRs) are expressed in different tissues, and VEGF‐VEGFR loops regulate a wide range of responses, including metabolic homeostasis, cell proliferation, migration and tubuleogenesis. As ligands, VEGFs act on three structurally related VEGFRs (VEGFR1, VEGFR2 and VEGFR3 [also termed FLT1, KDR and FLT4, respectively]) that deliver downstream signals. Haematopoietic stem cells (HSCs), megakaryocytic cell lines, cultured megakaryocytes (MKs), primary MKs and abnormal MKs express and secrete VEGFs. During the development from HSCs to MKs, VEGFR1, VEGFR2 and VEGFR3 are expressed at different developmental stages, respectively, and re‐expressed, e.g., VEGFR2, and play different roles in commitment, differentiation, proliferation, survival and polyplodization of HSCs/MKs via autocrine, paracrine and/or even intracrine loops. Moreover, VEGFs and their receptors are abnormally expressed in MK‐related diseases, including myeloproliferative neoplasms, myelodysplastic syndromes and acute megakaryocytic leukaemia (a rare subtype of acute myeloid leukaemia), and they lead to the disordered proliferation/differentiation of bone marrow cells and angiogenesis, indicating that they are closely related to these diseases. Thus, targeting VEGF‐VEGFR loops may be of potential therapeutic value.
Source: British Journal of Haematology - Category: Hematology Authors: Tags: Review Source Type: research

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Publication date: Available online 9 November 2017 Source:Seminars in Cancer Biology Author(s): Christian Flotho, Sebastian Sommer, Michael Lübbert Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiv...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Genetic alterations, including mutations and copy-number alterations, are central to the pathogenesis of myelodysplastic syndromes and related diseases (myelodysplasia), but their roles in allogeneic stem cell transplantation have not fully been studied in a large cohort of patients. We enrolled 797 patients who had been diagnosed with myelodysplasia at initial presentation and received transplantation via the Japan Marrow Donor Program. Targeted-capture sequencing was performed to identify mutations in 69 genes, together with copy-number alterations, whose effects on transplantation outcomes were investigated. We identifi...
Source: Blood - Category: Hematology Authors: Tags: Transplantation, Plenary Papers, Free Research Articles, Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: Hematopoiesis and Stem Cells, Pediatric Hematology, Free Research Articles, Myeloid Neoplasia, Phagocytes, Granulocytes, and Myelopoiesis, Red Cells, Iron, and Erythropoiesis, Review Articles, Review Series Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Review Articles, Review Series Source Type: research
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Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: How I Treat, Free Research Articles, Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
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Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
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Source: Annals of Hematology - Category: Hematology Source Type: research
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Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
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Source: Mayo Clinic Proceedings - Category: Internal Medicine Authors: Tags: Symposium on Neoplastic Hematology and Medical Oncology Source Type: research
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