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JAK2 Exon (jak2 + exon)
Selected AbstractsThe analysis of JAK2 and MPL mutations and JAK2 single nucleotide polymorphisms in MPN patients by MassARRAY assayINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2010S.-J. ZHANG Summary Recent studies have shown that JAK2 V617F, MPL W515L/K and JAK2 exon 12 mutations underlie the major molecular pathogenesis of myeloproliferative disorders (MPN). Allele-Specific Polymerase Chain Reaction (AS-PCR), direct sequencing and MassARRAY assay were used to ascertain the real prevalence of these mutations and the influence of genetic susceptibility in Chinese MPN patients. The positive rate of JAK2 V617F in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) was 82.0%, 36.6% and 51.1% respectively. One ET patient and two PMF patients harboured the MPL W515L mutation and three PV patients harboured JAK2 exon 12 mutations. All of these patients were confirmed as JAK2 V617F negative. Clinical data demonstrated that PV patients with JAK2 exon 12 mutations were younger, had higher haemoglobin levels and white blood cell counts than PV patients with JAK2 V617F. In addition, through analysis of 4 polymorphic loci of JAK2 gene, no significant difference of distribution frequency was found among PV, ET and PMF patients. Distribution frequency of haplotype also was not significantly different among PV, ET and PMF patients. We conclude that JAK2 V617F is a major molecular pathogenesis in Chinese MPN patients. MPL W515L mutation and JAK2 exon 12 mutations can also be found in JAK2 V617F negative MPN patients. [source] Isolated erythrocytosis in V617F negative patients with JAK2 exon 12 mutations: Report of a new mutationAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Martina Bernardi No abstract is available for this article. [source] Phospho-STAT5 and phospho-Akt expression in chronic myeloproliferative neoplasmsBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2009Lizz F. Grimwade Summary The majority of Myeloproliferative Neoplasms (MPNs) are characterised by mutations in genes encoding molecules or receptors involved in cell signalling, the most common being the JAK2 V617F mutation. This mutation leads to ligand-independent activation of downstream signalling pathways by constitutive phosphorylation. The signalling pathways affected include the Janus kinase-signal transducers and activators of transcription (JAK-STAT) and phosphotidylinositide-3 kinase (PI3K) pathways, which regulate cell survival and apoptosis respectively. Monoclonal antibodies to phospho-STAT5 and phospho-Akt were generated and assessed by immunocytochemistry on bone marrow biopsies of MPN patients with JAK2 V617F, JAK2 exon 12, MPL exon 10 and KIT D816V mutations. JAK2 V617F mutation was associated with significantly increased levels of phosphorylated STAT5 and Akt in haemopoietic cells, most marked in megakaryocytes. In contrast, JAK2 exon 12 and MPL exon 10 mutations did not affect the level of phosphorylation. In systemic mastocytosis with KIT D618V mutation there was significantly increased expression of phosphorylated STAT5 and Akt in neoplastic mast cells although there was no change in the expression in other haemopoietic cells. JAK2 V617F is associated with upregulated phosphorylation of STAT5 and Akt in megakaryocytes, and to a lesser extent in other haemopoietic cells. Immunocytochemistry of bone marrow trephines for these phospho-proteins can be used as a supplementary diagnostic test with a high negative predictive value. [source] Loss of the JAK2 intramolecular auto-inhibition mechanism is predicted by structural modelling of a novel exon 12 insertion mutation in a case of idiopathic erythrocytosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Elena Albiero Summary We report a novel gain-of-function JAK2 exon 12 insertion mutation in a patient with idiopathic erythrocytosis and low serum erythropoietin level. To date, only rare cases of such mutations have been reported in the JAK2 exon 12. Using computer-based structural modelling we propose that this mutation causes the loss of the JAK2 auto-inhibition step, leading to the constitutive activation of JAK2 tyrosine kinase-dependent activity. Our model-based hypothesis provides a useful approach for the investigation of the phenotype-genotype relationship in myeloproliferative disorders involving JAK2. [source] | ||||||||||