Primary Myelofibrosis
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
These include: i) more pronounced expression of phosphoSTAT5 protein in patients with JAK2V617F mutation compared to patients with wild-type of JAK2 kinase ii) different expression pattern of pSTAT5 in the nucleus and the cytoplasm of megakaryocytes and other bone marrow cells; iii) approximately 5-fold higher expression level of STAT5a gene in PV in comparison to patients with PMF and approximately 2-fold higher than in ET patients; iv) different, intracellular expression patterns of ERK2 and ERK1/2 antigens allowed to distinguish each subtype of MPN.
|
28260027 |
2017 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Prevalence of CALR mutation in JAK2-negative PMF and ET was 60.9% (14/23) and 75% (6/8), respectively.
|
31478923 |
2019 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients.
|
26163633 |
2015 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Moreover, 4 therapeutic JAK2 inhibitors (ruxolitinib, fedratinib, momelotinib, and pacritinib) have either been approved or are in advanced clinical development for myelofibrosis.
|
31560729 |
2019 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
JAK2 mutation analysis is now a formal component of diagnostic criteria for PV, ET, and PMF, but its prognostic utility is limited.
|
21220604 |
2011 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We investigated this question using conditional JAK2(V617F) knock-in mice with constitutive and inducible expression of JAK2(V617F) in hematopoietic cells, which develop a polycythemia vera (PV)-like disorder evolving into myelofibrosis.
|
24951423 |
2014 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The recent discovery of CALR mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients without JAK2/MPL mutations has emerged as a relevant finding for the molecular diagnosis of these myeloproliferative neoplasms (MPN).
|
25068507 |
2014 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Primary myelofibrosis or myelofibrotic transformation preceded all 7 JAK2-mutant but only 1 of 9 JAK2 wild-type AMLs (P = .001), implying that JAK2-mutant AML is preceded by mutation(s) that give rise to a "myelofibrosis" phenotype.
|
20008300 |
2010 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Megakaryocyte clustering was much less pronounced in the CIMF cases with mutant JAK2, with an analogous trend occurring in the ET cases.
|
17875526 |
2007 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
An acquired V617F mutation in JAK2 occurs in most patients with polycythaemia vera, but is seen in only half those with essential thrombocythaemia and idiopathic myelofibrosis.
|
16325696 |
2005 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway.
|
29123956 |
2017 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
When present in a heterozygous state the JAK2-V617F mutation preferentially stimulates megakaryopoiesis and in most cases manifests as essential thrombocythemia (ET), whereas homozygous JAK2-V617F reduces megakaryopoiesis in favor of increased erythropoiesis, resulting in polycythemia vera and/or myelofibrosis.
|
20008195 |
2009 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
We investigated the therapeutic potential of ruxolitinib, a JAK1/JAK2 inhibitor that has been FDA-approved for the treatment of myelofibrosis, to treat ovarian cancer either alone or in combination with conventional chemotherapy agents.
|
29849942 |
2018 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Although somatic mutations in <i>JAK2</i>, <i>MPL</i>, and <i>CALR</i> have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients.
|
28405618 |
2017 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Ruxolitinib is a dual janus kinase 1 (JAK1)/JAK2 inhibitor used to treat splenomegaly and symptoms associated with myelofibrosis (MF).
|
28260257 |
2017 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The JAK2 mutation was detected in 25 patients (46%); 12 of 26 patients with essential thrombocythemia (ET), 9 of 12 patients with polycyhtemia vera (PV), one of 7 patients with chronic idiopathic myelofibrosis (CIM) and one patient with unclassifiable MPD.
|
17249502 |
2006 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Primary Myelofibrosis (PMF) is a myeloproliferative disorder associated with JAK2V617F, Calreticulin (CALR) indels, and MPLW515L/K mutations activating the tyrosine kinase JAK2 and its downstream signaling pathway.
|
31369569 |
2019 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
The mutational spectrum in myelofibrosis includes driver mutations in genes such as JAK2, calreticulin, and myeloproliferative leukemia virus oncogene.
|
25635755 |
2015 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
In light of the approval of a JAK1/JAK2 inhibitor for the treatment of myelofibrosis, and preliminary studies evaluating the efficacy of other JAK inhibitors, the therapeutic potential of compounds that target JAK/STAT signalling in the treatment of patients with lymphoma is also discussed.
|
26123794 |
2015 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
LHGDN |
Control experiments showed that 10 indolent SM patients without associated MPD did not carry the JAK2 mutation V617F and that 15 CIMF patients without SM did not carry the KIT mutation D816V.
|
18165278 |
2008 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
LHGDN |
Concurrent JAK2(V617F) mutation and BCR-ABL translocation within committed myeloid progenitors in myelofibrosis.
|
17476275 |
2007 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A point mutation in exon 14 of the JAK2 gene resulting in the formation of the JAK2 V617F transcript occurs in 95% of PV patients and around 50% of ET and PMF patients driving constitutive activation of the JAK/STAT pathway.
|
30558676 |
2018 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
In fact, clinical trials of these compounds have demonstrated improvements in constitutional symptoms and splenomegaly in patients with both mutated and wild-type JAK2 MF.
|
22583424 |
2012 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Acquired familial Mediterranean fever associated with a somatic MEFV mutation in a patient with JAK2 associated post-polycythemia myelofibrosis.
|
26123310 |
2015 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Given that the identical somatic activating mutation in the JAK2 tyrosine kinase gene (JAK2(V617F)) is observed in most individuals with polycythemia vera, essential thrombocythemia and primary myelofibrosis, there likely are additional genetic events that contribute to the pathogenesis of these phenotypically distinct disorders.
|
19287384 |
2009 |