|
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 |
|
Myelofibrosis
|
0.900 |
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 |
|
Myeloproliferative disease
|
0.500 |
GeneticVariation
|
group |
BEFREE |
The single transmembrane domain (TMD) of the human thrombopoietin receptor (TpoR/MPL), encoded by exon 10 of the MPL gene, is a hotspot for somatic mutations associated with myeloproliferative neoplasms (MPNs).
|
31697803 |
2020 |
|
Myeloproliferative disease
|
0.500 |
Biomarker
|
group |
BEFREE |
Studies have shown that mutant calreticulin (CALR) constitutively activates the thrombopoietin (TPO) receptor MPL and thus plays a causal role in the development of myeloproliferative neoplasms (MPNs).
|
31462733 |
2020 |
|
Thrombocythemia, Essential
|
0.500 |
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 |
|
Chronic myeloproliferative disorder
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Collectively, cell-autonomous and constitutive activation of MPL is a cause of MPNs that are mediated by mutant CALR.
|
31848992 |
2020 |
|
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We found examples of both of these categories in published and previously unpublished MPL exon 10 sequencing data from MPN patients, demonstrating that some, if not all of the new mutations reported here represent likely drivers or modifiers of myeloproliferative disease.
|
31697803 |
2020 |
|
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia.
|
31741139 |
2020 |
|
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Based on these findings, we propose a model in which mutant CALR induces MPL activation on the cell surface to promote MPN development.
|
31462733 |
2020 |
|
MYELODYSPLASTIC SYNDROME
|
0.500 |
GeneticVariation
|
group |
BEFREE |
These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia.
|
31741139 |
2020 |
|
Thrombocytopenia
|
0.400 |
Biomarker
|
phenotype |
BEFREE |
Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, increases the platelet production, and are being increasingly used in various conditions with thrombocytopenia.
|
31830528 |
2020 |
|
Myelodysplasia
|
0.120 |
GeneticVariation
|
disease |
BEFREE |
These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia.
|
31741139 |
2020 |
|
Acute leukemia
|
0.110 |
GeneticVariation
|
disease |
BEFREE |
These mutations include JAK2, CALR and MPL mutations as the main disease drivers, mutations driving clonal expansion, and mutations that contribute to progression of chronic MPNs to myelodysplasia and acute leukemia.
|
31741139 |
2020 |
|
Autoimmune thrombocytopenia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Eltrombopag (ELT) is a thrombopoietin receptor activator that has shown efficacy in chronic immune thrombocytopenia.
|
31205222 |
2020 |
|
Autoimmune thrombocytopenia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists.
|
31280643 |
2020 |
|
Autoimmune thrombocytopenia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Romiplostim (Nplate<sup>®</sup>), a thrombopoietin receptor agonist, is the first FDA-approved thrombopoiesis-stimulating protein for the treatment of low platelet (PLT) counts in adults with chronic immune thrombocytopenia.
|
31021662 |
2020 |
|
Autoimmune thrombocytopenia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Markers of endothelial cell activation and neutrophil extracellular traps are elevated in immune thrombocytopenia but are not enhanced by thrombopoietin receptor agonists.
|
31805421 |
2020 |
|
Thrombocytopenia due to platelet alloimmunization
|
0.100 |
Biomarker
|
disease |
BEFREE |
Eltrombopag (ELT) is a thrombopoietin receptor activator that has shown efficacy in chronic immune thrombocytopenia.
|
31205222 |
2020 |
|
Thrombocytopenia due to platelet alloimmunization
|
0.100 |
Biomarker
|
disease |
BEFREE |
Markers of endothelial cell activation and neutrophil extracellular traps are elevated in immune thrombocytopenia but are not enhanced by thrombopoietin receptor agonists.
|
31805421 |
2020 |
|
Thrombocytopenia due to platelet alloimmunization
|
0.100 |
Biomarker
|
disease |
BEFREE |
Romiplostim (Nplate<sup>®</sup>), a thrombopoietin receptor agonist, is the first FDA-approved thrombopoiesis-stimulating protein for the treatment of low platelet (PLT) counts in adults with chronic immune thrombocytopenia.
|
31021662 |
2020 |
|
Thrombocytopenia due to platelet alloimmunization
|
0.100 |
Biomarker
|
disease |
BEFREE |
Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists.
|
31280643 |
2020 |
|
Immune thrombocytopenic purpura
|
0.100 |
Biomarker
|
disease |
BEFREE |
We aimed to explore the differential expression of miRNAs in patients with ITP before and after starting treatment with thrombopoietin-receptor agonists (TPO-RAs) to clarify their roles in the pathophysiology of ITP, and as potential diagnostic and prognostic markers of this disorder.
|
30885035 |
2020 |
|
Immune thrombocytopenic purpura
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP).
|
31146647 |
2020 |
|
Immune thrombocytopenic purpura
|
0.100 |
Biomarker
|
disease |
BEFREE |
Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists.
|
31280643 |
2020 |