A number of engineered or disease-associated TpoRs such as TpoR/MPL R102P, which causes congenital thrombocytopenia, are rescued for traffic and function by mutant CALRs, which can also overcome endoplasmic reticulum retention signals on TpoR.
Another patient with stroke and a pulmonary embolism was heterozygous for the p.Pro106Leu variant of the MPL gene, which has been associated with thrombocytosis.
Here we report unique familial cases of CAMT that presented with a previously unreported <i>MPL</i> mutation: T814C (W272R) in the background of the activating <i>MPL</i> G117T (K39N or Baltimore) mutation.
The thrombopoietin receptor (MPL) has been shown to be mutated (MPL W515L) in myelofibrosis and thrombocytosis yet new approaches to treat this disorder are still required.
To analyze the relationship between six polymorphisms in genes related to oxidative stress, namely CAT-262 C>T, MnSOD Ala16Val, GPX1 Pro198Leu, GSTM1 and GSTT1 null genotypes, and GSTP1 Ile105Val, and the occurrence of BCR-ABL negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis).
Retrospective molecular studies detected a MPL W515S homozygous mutation in both the initial and remission marrows for B-ALL, at 30-40% and 80% dosage effect, respectively.
Retrospective molecular studies detected a MPL W515S homozygous mutation in both the initial and remission marrows for B-ALL, at 30-40% and 80% dosage effect, respectively.
Retrospective molecular studies detected a MPL W515S homozygous mutation in both the initial and remission marrows for B-ALL, at 30-40% and 80% dosage effect, respectively.
More importantly, we demonstrated that this MPL Y252H mutant confers increased TPO/MPL-mediated cell growth and increased cell survival upon cytokine withdrawal in BaF3 cells, indicating it is a disease-driving mutation and may contribute to the development of ET in vivo.
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.
In a group of 36 Mexican mestizo patients with MPN, we studied five molecular markers: The BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPL W515L mutation and the MPL W515K mutation; 17 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary mielofibrosis (MF), five with undifferentiated MPN, one with primary erythrocytosis and one with familial thrombocytosis.
In contrast to cells expressing the parental MPL(W515L), MPL(W515L)-KDEL-expressing FDC-P1 cells were unable to grow autonomously and to produce tumors in nude mice.
In a group of 36 Mexican mestizo patients with MPN, we studied five molecular markers: The BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPL W515L mutation and the MPL W515K mutation; 17 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary mielofibrosis (MF), five with undifferentiated MPN, one with primary erythrocytosis and one with familial thrombocytosis.
In a group of 36 Mexican mestizo patients with MPN, we studied five molecular markers: The BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPL W515L mutation and the MPL W515K mutation; 17 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary mielofibrosis (MF), five with undifferentiated MPN, one with primary erythrocytosis and one with familial thrombocytosis.
We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation.
We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation.
We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation.
MPL W515L mutation was found to be harbored in only one of 102 patients, who had essential thrombocythemia (ET, 1.0%) and was not detected in patients with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML).