Abstract
Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm resulting from an acquired driver mutation in the JAK2 gene of hematopoietic stem and progenitor cells resulting in the overproduction of mature erythrocytes and abnormally high hematocrit, in turn leading to thromboembolic complications. Therapeutic phlebotomy is the most common treatment to reduce the hematocrit levels and consequently decrease thromboembolic risk. Here we demonstrate that, by using the iron restrictive properties of the antisense oligonucleotides against Tmprss6 mRNA, we can increase hepcidin to achieve effects equivalent to therapeutic phlebotomy. We provide evidence that this less invasive approach could represent an additional therapeutic tool for the treatment of PV patients.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Humans
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Janus Kinase 2 / genetics
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Janus Kinase 2 / metabolism
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice, Transgenic
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Oligonucleotides, Antisense / genetics
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Oligonucleotides, Antisense / pharmacology*
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Polycythemia Vera / drug therapy*
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Polycythemia Vera / genetics
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Polycythemia Vera / metabolism
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism
Substances
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Membrane Proteins
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Oligonucleotides, Antisense
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RNA, Messenger
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Jak2 protein, mouse
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Janus Kinase 2
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Serine Endopeptidases
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matriptase 2