rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The advances in molecular insights, especially the discovery of the Janus kinase 2 (JAK2) V617F mutation and its role in JAK-STAT pathway dysregulation, led to the development of the JAK inhibitor ruxolitinib, which currently represents the cornerstone of medical therapy in MF and hydroxyurea-resistant/intolerant PV.
|
31228096 |
2019 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
With the advent of targeted therapies, such as the Janus kinase inhibitors, many patients have experienced substantial clinical benefits, including reduction in splenomegaly and symptoms and, in some instances, improvement or stabilization of bone marrow fibrosis and reduction of JAK2 V617F allele burden.
|
30343328 |
2019 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF.JAK2 V617F was mutated in 61%.
|
30408564 |
2019 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
A JAK2 variant in addition to JAK2 V617F (n = 13) in myelofibrosis was associated with an increased cumulative risk of transformation into AML (P = .003).
|
30811597 |
2019 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
To identify key features that may help distinguish these 2 entities, we retrospectively studied 21 cases diagnosed as "CMML" with JAK2 V617F and bone marrow fibrosis that were identified from a cohort of 610 cases of CMML diagnosed in 2006 to 2016.
|
30447300 |
2019 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Overall response rates (ORRs) in patients with JAK2 V617F-mutated PV, ET, and MF were 95%, 90.5%, and 9.1%, respectively, while patients with ET and MF without the JAK2 V617F mutations had ORRs of 43.7% and 0%, respectively.
|
30025280 |
2018 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
JAK2 V617F mutation in plasma cell-free DNA preceding clinically overt myelofibrosis: Implications for early diagnosis.
|
29565699 |
2018 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Collectively, our studies demonstrate that occasional patients with CALR mutation-positive ET or MF carry other MPN-initiating genetic mutations (including JAK2 V617F), acquire "secondary mutations" before or after the CALR mutation, or evolve over time to being CALR mutation-homozygous.
|
28168700 |
2017 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF.
|
28395559 |
2017 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Since the discovery of the activating V617F mutation in Janus kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis.
|
28441920 |
2017 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013.
|
25870379 |
2015 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Activation of Janus kinase 2 (JAK2), frequently as a result of the JAK2(V617F) mutation, is a characteristic feature of the classical myeloproliferative neoplasms (MPNs) polycythemia vera, essential thrombocythemia, and myelofibrosis, and it is thought to be responsible for the constitutional symptoms associated with these diseases.
|
25912019 |
2015 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, leukocyte counts, hemoglobin, and hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F-positive essential thrombocythemia.
|
25934766 |
2015 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis.
|
26228487 |
2015 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Around 50% of patients with myelofibrosis have the JAK2(V617F) mutation, but almost all patients have aberrant activation of the JAK-STAT signalling pathway.
|
26648193 |
2015 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The discovery of the activating JAK2 V617F mutation in patients with myelofibrosis (MF) led to the development of JAK2 inhibitors.
|
24856675 |
2014 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
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 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
JAK2 V617F mutations were detected in 6 of the 28 patients with bone marrow fibrosis presenting at the time of diagnosis and 2 of the 7 patients with bone marrow fibrosis developing in the course of disease, significantly higher than the control group patients.
|
24186132 |
2014 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Here, we show that treatment with the dual phosphoinositide-3-kinase (PI3K)/AKT and mTOR inhibitor BEZ235 attenuated PI3K/AKT and mTOR signaling, as well as induced cell-cycle growth arrest and apoptosis of the cultured human JAK2-V617F-expressing HEL92.1.7 (HEL), UKE1 cells, and primary CD34+ myelofibrosis (MF)-MPN cells.
|
23445613 |
2013 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
Given their diagnostic relevance, it is also beneficial and relatively straightforward to screen JAK2 V617F negative patients for JAK2 exon 12 mutations (in the case of erythrocytosis) or MPL exon 10 mutations (thrombocytosis or myelofibrosis) using appropriate assays.
|
23057517 |
2013 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The chronic myeloproliferative neoplasms (MPNs), are characterized by a Janus Kinase (JAK)-2 V617F point mutation but this molecular abnormality does not explain by itself the pathogenesis of these disorders, or the phenotypic diversity associated with essential thrombocythemia, polycythemia vera (PV), and myelofibrosis.
|
24290217 |
2013 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
There was a trend toward a more frequent evolution to myelofibrosis when the JAK2(V617F) mutated allele burden was >50% (p=0.09), but not to AML.
|
22818858 |
2013 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
These standards were used in two JAK2 p.V617F assays, which were used to support clinical studies of ruxolitinib (Jakafi(®)) in myelofibrosis, a real-time polymerase chain reaction assay for initial screening of all samples, and a novel single-nucleotide polymorphism typing (SNaPshot)-based assay for samples with less than 5% mutant allele burden.
|
23537216 |
2013 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
The most prevalent mutation identified is a gain-of-function mutation in the Janus kinase (JAK) family, JAK2 V617F, which has been identified in more than half of patients with myelofibrosis.
|
23307549 |
2013 |
rs77375493
|
JAK2;INSL6
|
Myelofibrosis
|
|
0.100 |
GeneticVariation |
BEFREE |
However, JAK2 inhibitors have limited ability to reduce JAK2 V617F allele burden or bone marrow fibrosis in humans.
|
23313046 |
2013 |