Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
"Driver" mutations in JAK2, MPL and indels in CALR underlie the vast majority of cases of PMF and post-ET MF; the remainder (≈ 10%) lack identifiable driver mutations, but other clonal markers are usually detectable.
|
31630335 |
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 |
AlteredExpression
|
disease |
BEFREE |
The discovery of mutations in JAK2, CALR, and MPL have uncovered activated JAK-STAT signaling as a primary driver of MF, supporting a rationale for JAK inhibition.
|
31511492 |
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 |
Biomarker
|
disease |
BEFREE |
Calreticulin (CALR) mutation was identified as a recurrent mutation in about 60% to 88% of JAK2/MPL-negative PMF and ET.
|
31478923 |
2019 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Immune thrombocytopenia is associated with persistently deranged fibrosis-related seromarker profiles but low bone marrow fibrosis grades: A 2-year observational study on thrombopoietin receptor agonist treatment.
|
29293383 |
2019 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Only about 10% of patients with myelofibrosis harbor alterations in MPL gene.
|
31446640 |
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 |
In fact, exome sequencing revealed that most patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) lacking JAK2 or MPL mutations, harbor somatic insertion and/or deletion in exon 9 of CALR gene.
|
28340692 |
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 |
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 |
The frequency of the MPL mutation was 0% in PV, from 0.9 to 12.5% in ET, and from 0 to 17.1% in PMF.
|
31208359 |
2019 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Besides the driver mutations in JAK2, MPL, and CALR genes, the deregulation of miRNA expression may also contribute to the pathogenesis of PMF.
|
30259659 |
2018 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutations in CALR or MPL are present as driving mutations in the majority of remaining ET and PMF patients.
|
30558676 |
2018 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Oncogenic driver mutations in PMF include Janus kinase 2, calreticulin (CALR), and myeloproliferative leukemia virus oncogene.
|
29256926 |
2018 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations.
|
29515238 |
2018 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional disease features include bone marrow stromal reaction including reticulin fibrosis, abnormal cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.
|
30039550 |
2018 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Correction: Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.
|
30232464 |
2018 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes.
|
29047144 |
2018 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL-unmutated ET and primary myelofibrosis.
|
28415571 |
2017 |
Primary Myelofibrosis
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
|
28622305 |
2017 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
Conversely, elimination of macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of the murine model, suggesting that fibrocyte differentiation induced by MPL activation contributes to the progression of MF.
|
28386106 |
2017 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
We screened 136 patients with myelofibrosis and a median age of 58 years who underwent allogeneic stem cell transplantation (AHSCT) for molecular residual disease for JAKV617F (n=101), thrombopoietin receptor gene (MPL) (n=4) or calreticulin (CALR) (n=31) mutation in peripheral blood on day +100 and +180 after AHSCT.
|
28714945 |
2017 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Activating point mutations in the MPL gene encoding the thrombopoietin receptor are found in 3%-10% of essential thrombocythemia (ET) and myelofibrosis patients.
|
28395806 |
2017 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
A 65-year-old woman with MPL-mutated essential thrombocythemia and progression to myelofibrosis was noted upon routine pretransplant testing to have mixed field reactivity with anti-D and an historic discrepancy in RhD type.
|
28653329 |
2017 |