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.
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.
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.
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.
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.
Further investigations for intracoronary thrombus with no underlying atherosclerotic disease revealed positive Janus kinase 2 (JAK2) V617F gene mutation, and this was consistent with a diagnosis of ET with elevated platelet count.
The thrombopoietin receptor (MPL) has been shown to be mutated (MPLW515L) in myelofibrosis and thrombocytosis yet new approaches to treat this disorder are still required.
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.
Recently, germline mutations in Janus kinase 2 (JAK2) and MPL, two genes frequently mutated in sporadic MPD, have been shown to cause inherited thrombocytosis.
In light of the findings from previous reports, screening for the JAK2-V617F mutation should be considered for any Ph(+) CML patients with thrombocytosis, leukocytosis, or erythrocytosis at diagnosis and for patients who subsequently develop thrombocytosis, leukocytosis, or erythrocytosis during follow-up, even for CML patients in complete cytogenetic response and major molecular response.
A 66-year-old man who presented with progressive and marked thrombocytosis but normal hemoglobin was diagnosed to have essential thrombocythemia upon the demonstration of JAK2V617F mutation.
A decrease in expression of the Mpl protein can cause thrombocytosis even in the absence of mutations in the coding sequence, due to a shift in the balance between stimulation of signaling in megakaryopoiesis and removal of thrombopoietin by receptor mediated internalization in platelets.
The observed biological difference in circulating granulocyte involvement by the JAK2V617F clone necessitates a sensitive molecular assay for the diagnostic investigation of thrombocytosis.