Experimental hematology
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Experimental hematology · Nov 2007
Phenotypic variations and new mutations in JAK2 V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis.
The chronic myeloproliferative disorders (MPD), polycythemia vera (PV), essential thrombocytosis, and idiopathic myelofibrosis (IMF), are characterized by a spectrum of clinical features and linked by common genetic lesions in JAK2 and MPL. However, the clinical phenotypes in genetically undefined MPD patients are similar to those patients with JAK2 and MPL lesions. We, therefore, sought to determine whether there were JAK2 or MPL lesions in a well-defined, JAK2 V617F-negative MPD cohort, and to determine if clinical associations could be identified based on variations identified in these genes. ⋯ While the clinical phenotype of JAK2 exon 12 lesions in the MPD was predominantly erythroid, there was significant disease spectrum overlap between JAK2 V617F and JAK2 exon 12 mutations. By contrast, MPL gene mutations were not associated with erythrocytosis, but segregated primarily with the phenotypes of thrombocytosis, extramedullary disease, myelofibrosis, and osteosclerosis.
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Experimental hematology · Nov 2007
Regulated expression of microRNAs in normal and polycythemia vera erythropoiesis.
Polycythemia vera (PV) is a myeloproliferative disorder, arising from the acquired mutation(s) of a hematopoietic stem cell. The JAK2 V617F somatic mutation is found in most PV patients; however, it is not the disease-initiating mutation. Because microRNAs (miRNAs) play a regulatory role in hematopoiesis, we studied miRNA expressions in PV and normal erythropoiesis. ⋯ We identified the miRNAs with regulated expression in erythropoiesis; one appeared to be PV-specific. Their miRNA expression levels define early, intermediate, and late stages of erythroid differentiation. The validity of our findings was confirmed in nonexpanded peripheral blood cells.
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Experimental hematology · Jul 2007
Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors.
Endothelial progenitor cells (EPCs) are used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk. However, there is no uniform definition of an EPC, which confounds EPC studies. EPCs are widely described as cells that coexpress the cell-surface antigens CD34, AC133, and vascular endothelial growth factor receptor-2 (VEGFR-2). These antigens are also expressed on primitive hematopoietic progenitor cells (HPCs). Remarkably, despite their original identification, CD34+AC133+VEGFR-2+ cells have never been isolated and simultaneously plated in hematopoietic and endothelial cell (EC) clonogenic assays to assess the identity of their clonal progeny, which are presumably the cellular participants in vascular regeneration. ⋯ Therefore, CD34+AC133+VEGFR-2+ cells are HPCs that do not yield EC progeny, and the biological mechanism for their correlation with cardiovascular disease needs to be reexamined.
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Experimental hematology · Jun 2007
Clinical TrialComparative analysis of naïve and memory CD4+ and CD8+ T-cell subsets in bone marrow and G-CSF-mobilized peripheral blood stem cell allografts: impact of donor characteristics.
Donor T cells expressing lymph node homing receptors are the foremost initiators of acute graft-vs-host disease (aGVHD), and a high proportion of CD4(+)CCR7(+) T cells in human leukocyte antigen-matched allografts has been shown to confer a high risk of aGVHD without interfering in other outcomes. ⋯ This study provides reference values for CD4(+) and CD8(+) naïve and memory subsets within allografts applicable to the healthy donor population and indicates that beforehand analysis of a whole-blood sample can help evaluating the risk of aGVHD conferred by each donor and, when possible, choosing the one conferring the lowest risk.
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Experimental hematology · Apr 2007
Biography Historical ArticleEugene P. Cronkite--The man and his science.