Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative disorders.
|
18669880 |
2008 |
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 |
GeneticVariation
|
disease |
BEFREE |
Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are myeloproliferative neoplasms characterized by recurrent somatic mutations in JAK2, CALR, and MPL.
|
27727468 |
2016 |
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 |
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 |
GeneticVariation
|
disease |
BEFREE |
Recent studies have also identified novel JAK2 and MPL mutations in patients with essential thrombocythemia and myelofibrosis (MF).
|
27913528 |
2016 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.
|
19713221 |
2010 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
BEFREE |
A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells.
|
27114459 |
2016 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We show that this antibody specifically recognized patients harboring different types of CALR mutation with no staining in healthy controls and JAK2- or MPL-mutated ET and PMF.
|
24618731 |
2014 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis.
|
17709604 |
2007 |
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 |
SomaticCausalMutation
|
disease |
ORPHANET |
DNA sequence analysis of the exons encoding the transmembrane and juxtamembrane domains of EPOR, MPL, and GCSFR, and comparison with germline DNA derived from buccal swabs, identified a somatic activating mutation in the transmembrane domain of MPL (W515L) in 9% (4/45) of JAKV617F-negative MF.
|
16834459 |
2006 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
MPL(W515L) was found in 3% of ET and 8% of PMF, with a significantly higher percentage of mutated alleles in fibrotic than prefibrotic PMF (median, 78% MPL(W515L) alleles; p<0.05).
|
19616600 |
2009 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We conclude that MPL(W515L) occurs in a considerable proportion of acute megakaryoblastic leukaemias with myelofibrosis unrelated to PMF.
|
19194467 |
2009 |
Primary Myelofibrosis
|
1.000 |
Biomarker
|
disease |
CTD_human |
|
|
|
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 |
More recently, another mutation in the juxtamembrane domain of the thrombopoietin receptor Mpl was discovered in about 5% of patients with CIMF and ET.
|
18220909 |
2007 |
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 |
In addition, a mutation of the thrombopoietin receptor, MPLW515L, has been documented in some patients with IMF.
|
17222772 |
2007 |
Primary Myelofibrosis
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) constitute the BCR-ABL1-negative myeloproliferative neoplasms and are characterized by mutually exclusive Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) mutations; respective frequencies of these mutations are approximately 95%, 0%, and 0% in PV, 60%, 20%, and 3% in ET, and 60%, 25%, and 7% in PMF.
|
26182311 |
2015 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
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 |
Primary Myelofibrosis
|
1.000 |
GeneticVariation
|
disease |
CLINVAR |
New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition.
|
18528423 |
2008 |
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 |
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 |
Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF.
|
18451306 |
2008 |