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We found examples of both of these categories in published and previously unpublished MPL exon 10 sequencing data from MPN patients, demonstrating that some, if not all of the new mutations reported here represent likely drivers or modifiers of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 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Myeloproliferative neoplasms (MPNs) are associated with somatic mutations of genes including JAK2, CALR, or MPL in hematopoietic stem cells.
|
31377025 |
2019 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Mutations in <i>CALR</i> observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) pathway.
|
31810292 |
2019 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
<b>Expert Opinion</b>: Altogether, we believe that MPL is an important, but challenging, therapeutic target in MPNs that requires novel strategies to interrupt the specific conformational changes induced by each mutation or pathologic interaction without compromising the key functions of wild type MPL.
|
31092065 |
2019 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Since its discovery in 2013, we now have a more precise understanding of how mutant CALR, an endoplasmic reticulum chaperone protein, activates the JAK/STAT signaling pathway via a pathogenic binding interaction with the thrombopoietin receptor, MPL, to induce MPN.
|
31562135 |
2019 |
Chronic myeloproliferative disorder
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Since association with MPL is required for the oncogenicity of mutant CALR, we propose a model in which the constitutive activation of the MPL downstream pathway by mutant CALR multimers induces the development of MPN.
|
29946189 |
2019 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Recent data demonstrated that the TPO receptor (MPL) is essential for the development of CALR mutant-driven Myeloproliferative Neoplasms (MPNs).
|
31332222 |
2019 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN.
|
28990497 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
The association between the <i>JAK2</i> haplotype<sup>GGCC_46/1</sup> and mutations in other genes, such as thrombopoietin receptor (<i>MPL</i>) and calreticulin (<i>CALR</i>), or the association with triple negative MPN, is still controversial.
|
29641446 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
This study explored the relationship between mutations in the Janus kinase 2 gene ( JAK2), MPL, and the calreticulin gene ( CALR) in Uygur and Han Chinese patients with BCR-ABL fusion gene-negative MPN and corresponding clinical features.
|
30084272 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
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 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs).
|
28411309 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs.
|
29741776 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
JAK2, CALR, MPL and triple-negative mutational status has a direct impact on symptom severity and disease burden assessed by MPN10 score in myeloproliferative neoplasms (MPNs).
|
28828906 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The discovery of the activating Janus kinase (JAK)2<sup>V617F</sup> mutation in 2005 in most patients with the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) spurred intense interest in research into these disorders, culminating in the identification of activating mutations in MPL in 2006 and indels in the gene encoding calreticulin (CALR) in 2013, thus providing additional mechanistic explanations for the universal activation of JAK-signal transducer and activator of transcription (JAK-STAT) observed in these conditions, and the success of the JAK1/2 inhibitor ruxolitinib, which first received regulatory approval in 2011.
|
29277359 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF.
|
29426921 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the ER chaperone calreticulin (CALR) are common in myeloproliferative neoplasm (MPN) patients, activate the thrombopoietin receptor (MPL), and mediate constitutive JAK/STAT signaling.
|
30429377 |
2018 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
MPN driver mutations (JAK2, CALR, MPL) are somatically acquired also in familial cases, so a genetic predisposition to acquire one of the MPN driver mutations would be inherited, even though the causative germline mutations underlying familial MPN remain largely unknown.
|
28444727 |
2017 |
Chronic myeloproliferative disorder
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The combination of laboratory testing for the detection of JAK2, CALR, and MPL mutations is necessary to improve the diagnosis and classification of BCR-ABL1-negative MPN.
|
28406068 |
2017 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Somatic mutations of Janus kinase 2 (JAK2V617F), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) are the major clonal molecules that drive the pathogenesis of myeloproliferative neoplasms (MPN).
|
28625126 |
2017 |
Chronic myeloproliferative disorder
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by myeloproliferative leukemia protein (MPL)-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34 cells, platelets and megakaryocytes.
|
27740635 |
2017 |
Chronic myeloproliferative disorder
|
0.500 |
Biomarker
|
disease |
BEFREE |
Acquiring mutations in JAK2/CALR/MPL or the BCR-ABL translocation probably drive the oncogenic phenotype towards a specific MPN.
|
28335073 |
2017 |