These results confirm the findings of two previous studies that thrombopoietin expression is not the main cause of thrombocytosis in the 3q21q26 syndrome.
The mutation was not found in three other unaffected cases from the family except in another proband's daughter who did not present thrombocytosis but had a high TPO level.
The recently characterized protein-protein interaction of CALR mutants and MPL receptor has advanced our knowledge on the functional role of CALR mutants in thrombocythemia but it has also uncovered limitations of the current established research models.
Thrombocytosis can be due to genetic alterations that affect either the intrinsic MPL signaling through gain-of-function (GOF) activity (<i>MPL, JAK2, CALR</i>) and loss-of-function (LOF) activity of negative regulators (<i>CBL, LNK</i>) or the extrinsic MPL signaling by <i>THPO</i> GOF mutations leading to increased TPO synthesis.
Recently, germline mutations in Janus kinase 2 (JAK2) and MPL, two genes frequently mutated in sporadic MPD, have been shown to cause inherited thrombocytosis.
Following the observation of thrombopoietin (TPO) gene abnormalities as the cause of familiar cases of thrombocythemia similar derangements of TPO and/or its receptor (c-mpl) might be surmised to be at the root of increased platelet count also in non-familiar (sporadic) cases.
IL-6 acts on hepatocytes to enhance the production of thrombopoietin, which in turn interacts with its cognate receptor c-MPL on megakaryocytes and bone marrow progenitor cells to promote their expansion and proliferation, resulting in reticulated thrombocytosis.
However, when a patient presents with isolated thrombocytosis and a positive JAK2V617F assay, particularly a young woman, the possibility of PV must always be considered because of plasma volume expansion.
Our results suggest that low expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, thereby promoting platelet production from megakaryocytes or their progenitors in bone marrow, resulting in the subsequent thrombocytosis in preterm infants.
We investigated the JAK2V617F, CALR and STAT5 activation status in patients with CML and thrombocytosis (CML-T) that mimicked ET, trying to identify a common mechanism for thrombocytosis in MPN.
Investigation for polycythaemia and thrombocytosis showed JAK2 positive myeloproliferative neoplasm.A diagnosis of AOP infarction is often missed or delayed because it is rare and presents with variable neurological symptoms.
Transgenic mice overexpressing human c-mpl ligand exhibit chronic thrombocytosis and display enhanced recovery from 5-fluorouracil or antiplatelet serum treatment.
In the case of a patient with erythrocytosis and other signs of myeloproliferation, such as leukocytosis, thrombocytosis or splenomegaly, the diagnosis of polycythemia vera (PV) is likely, and I test serum erythropoietin and JAK2 mutations first.
Refractory anemia with ring sideroblasts (RARS-T) associated with marked thrombocytosis is a myelodysplastic/myeloproliferative neoplasm associated with both SF3B1 and JAK2 or MPL mutations.
The contribution of increased TPO protein synthesis by a translational mechanism was recently appreciated as the cause for hereditary thrombocythemia and will have to be elucidated in other conditions of thrombocytosis in association with increased TPO levels.
Refractory anemia with ring sideroblasts (RARS-T) associated with marked thrombocytosis is a myelodysplastic/myeloproliferative neoplasm associated with both SF3B1 and JAK2 or MPL mutations.
His postoperative management included the examination of his peripheral blood as well as bone marrow, which confirmed that the cause of his elevated platelet count was due to JAK2V617F mutation that is treated by hydroxyurea and aspirin after being discharged from the hospital.
Age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis.