|
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Ruxolitinib, a selective JAK1/JAK2 inhibitor, is the current first line therapy for myelofibrosis (MF), which reduces symptomatology and splenomegaly, but does not clearly modify disease course.
|
31778911 |
2020 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Approximately 6% and 14% of JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients, respectively, have 'canonical' MPL exon 10 driver mutations W515L/K/R/A or S505N, which generate constitutively active receptors and consequent loss of Tpo dependence.
|
31697803 |
2020 |
|
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Conversely, mice carrying the hypomorphic Gata1<sup>low</sup> mutation express an activated TPO/JAK2 pathway and partially respond to JAK inhibitors in a fashion similar to PMF patients (reduction of spleen size but limited improvement of the natural history of the disease).
|
31749302 |
2020 |
|
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 |
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 |
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 |
In the current study, we have increased the number of informative cases from 130 to 414 (median age 63 years; 63% males), in order to revisit with the phenotypic and prognostic relevance of the JAK2 46/1 haplotype in PMF.
|
30516848 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
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 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We found that ASXL1 or EZH2 mutation acquisition after JAK2 leads to PV, while ASXL1 mutation acquisition before JAK2 leads to ET or PMF.
|
31704857 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We performed Sanger sequencing of exon 9 of CALR gene in blood samples obtained from 33 Moroccan patients with ET or PMF non-mutated for JAK2.
|
28340692 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We conclude that besides morphology of megakaryocytes and other features, JAK2 V617F allelic burden can help differentiate CMML from PMF with monocytosis.
|
30447300 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Fedratinib (INREBIC<sup>®</sup>) is a JAK2-selective inhibitor that has been developed as an oral treatment for myelofibrosis.
|
31571162 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Myelofibrosis in 2019: moving beyond JAK2 inhibition.
|
31511492 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
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 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Whether noncanonical and/or concomitant JAK2- and MPL-mutations exist in myelofibrosis (MF) regardless of phenotype-driver mutations is not yet elucidated.
|
31135094 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
ABSTRACT: Background The BCR-ABL-negative myeloproliferative neoplasms, i.e., polycythemia vera, essential thrombocythemia (ET), and myelofibrosis (MF), are characterized by mutations in JAK2, CALR, or MPL.
|
30889303 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
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 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
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 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Laboratory tests and bone marrow biopsy confirmed underlying systemic disease to be Janus kinase 2 mutation positive primary idiopathic myelofibrosis.
|
31164383 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Calreticulin (CALR) exon 9 frameshift mutations have recently been identified in 30-40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) without JAK2 or MPL mutations.
|
30080988 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
An integral part of laboratory tests carried out in this disease group is detecting the presence of mutations in the Janus kinase 2 gene at position 617 (JAK2 V617F) and in the gene encoding for the receptor for thrombopoietin (myeloproliferative leukemia virus oncogene, MPL) found in approximately 60% of PMF patients.
|
29534592 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
One hundred five Philadelphia-negative MPN patients, including polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF) were initially screened for JAK2 mutations by amplification-refractory mutation system (ARMS-PCR) methodology and were further subjected to detection of CALR gene mutations by our in-house assay, a PCR based amplicon length differentiation assay (PCR-ALDA).
|
31248375 |
2019 |
|
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Constitutive activation of JAK/STAT signaling through mutations in <i>JAK2, CALR</i>, or <i>MPL</i> is central to myelofibrosis pathogenesis.
|
30563936 |
2019 |
|
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 |
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 |