Linked Life Data

16384930

Source:http://linkedlifedata.com/resource/pubmed/id/16384930

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-4-21
pubmed:abstractText
Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by excessive erythrocyte production. Most patients with PV harbor an activating JAK2 mutation, but the molecular links between this mutation and erythrocyte overproduction are unknown. The interaction between death receptors and their ligands contributes to the physiological regulation of erythropoiesis through the inhibition of erythroblast proliferation and differentiation. With the use of an in vitro culture system to generate differentiating erythroid cells, we found that erythroblasts derived from patients with PV harboring the JAK2 V617F mutation were able to proliferate and generate higher numbers of mature erythroid cells in the presence of inhibitory signals delivered by CD95 (Fas/Apo-1) and TRAIL receptor stimulation. JAK2-mutated PV erythroblasts showed lower levels of CD95-induced caspase activation and incomplete caspase-mediated cleavage of the erythroid transcription factor GATA-1, which was entirely degraded in normal erythroblasts on CD95 stimulation. JAK2 mutation was associated in PV erythroblasts with cytokine-independent activation of the JAK2 effectors Akt/PKB and ERK/MAP and with a deregulated expression of c-FLIP(short), a potent cellular inhibitor of death receptor-induced apoptosis. These results show the presence in PV erythroblasts of proliferative and antiapoptotic signals that may link the JAK2 V617F mutation with the inhibition of death receptor signaling, possibly contributing to a deregulation of erythropoiesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3495-502
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16384930-Adult, pubmed-meshheading:16384930-Aged, pubmed-meshheading:16384930-Antigens, CD95, pubmed-meshheading:16384930-Apoptosis, pubmed-meshheading:16384930-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:16384930-Erythroid Precursor Cells, pubmed-meshheading:16384930-Erythropoiesis, pubmed-meshheading:16384930-Female, pubmed-meshheading:16384930-Gene Expression, pubmed-meshheading:16384930-Humans, pubmed-meshheading:16384930-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16384930-Janus Kinase 2, pubmed-meshheading:16384930-Male, pubmed-meshheading:16384930-Middle Aged, pubmed-meshheading:16384930-Mutation, pubmed-meshheading:16384930-Polycythemia Vera, pubmed-meshheading:16384930-Protein-Tyrosine Kinases, pubmed-meshheading:16384930-Proto-Oncogene Proteins, pubmed-meshheading:16384930-Receptors, Tumor Necrosis Factor
pubmed:year
2006
pubmed:articleTitle
Increased death receptor resistance and FLIPshort expression in polycythemia vera erythroid precursor cells.
pubmed:affiliation
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. a.zeuner@iss.it
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't