Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages in the bone marrow. The WHO classification describes six major groups of chronic myeloproliferative disorders, as follows: chronic myeloid leukemia, chronic neutrophilic leukemia, chronic eosinophilic leukemia, polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis. The diagnosis of chronic myeloid leukemia and certain types of chronic eosinophilic leukemia are based on the detection of fusion genes (in chronic myeloid leukemia the BCR/ABL fusion gene, and in chronic eosinophilic leukemia the FIP1L1-PDGFRalpha gene). On the other hand molecular markers for polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis were lacking, making it difficult to identify these disorders clearly. The authors investigated the incidence of the newly identified somatic point mutation V617F of the Janus-2 tyrosine kinase in patients with polycythemia vera, essential thrombocythemia and myelofibrosis. Janus-2 kinase is a cytoplasmic, non-receptor protein-tyrosine kinase with a key role in signal transduction from multiple hematopoietic growth factor receptors. The mutant protein is constitutively phosphorylated and is able to activate its downstream signaling pathways in the absence of any cytokine, thereby contributing to the pathogenesis of chronic myeloproliferative disorders. The authors investigated DNA samples from 132 patients with chronic myeloproliferative disorders. The V617F mutation was detected by allele-specific polymerase chain reaction, and the patients were genotyped by a DNA tetra-primer amplification refractory mutation system assay. Approximately 73% of polycythemia vera, 60% of essential thrombocythemia and 67% of myelofibrosis showed the JAK2 V617F mutation. Using the amplification refractory mutation system assay, the frequency of homozygotes was 17.5% in polycythemia vera, 5.4% in essential thrombocythemia and 0% in myelofibrosis. The authors established an effective polymerase chain reaction based method for the identification of JAK2 mutation in the routine oncohematologic diagnostics.
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PMID:[Novel method in diagnosis of chronic myeloproliferative disorders--detection of JAK2 mutation]. 1740 11

Classical BCR/ABL fusion gene negative myeloproliferative neoplasms (MPN), including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), are clonal hematopoietic malignancies sharing in common origin in a multipotential hematopoietic stem cell. The phenotypic variability of the three entities can not be elucidated by JAK2V617F mutation only. Recent discoveries indicated that JAK2V617F allele burden, other mutated genes (such as TET2, ASXL1) and inherited predisposition can play roles in the complicated pathogenesis of MPN, which are summarized in this review.
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PMID:[Research progress on molecular pathogenesis of myeloproliferative neoplasms]. 2136 61

A 68-year-old man complained of dizziness and was referred to our hospital by his primary physician for evaluation of an elevated leukocyte count. In April 2002, soon after the chronic phase of chronic myeloid leukemia had been diagnosed, he was treated with imatinib. In March 2010, imatinib treatment was completed and the BCR/ABL fusion gene had become undetectable by real time quantitative PCR. Subsequently, leukocyte counts and the hematocrit gradually rose. In August 2012, a bone marrow aspirate showed hypercellular marrow with marked erythroid hyperplasia and the presence of the JAK2 gene V617F mutation. He was diagnosed with polycythemia vera. Phlebotomy and chemotherapy were started in addition to imatinib administration. Shortly thereafter complete blood counts returned to normal levels.
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PMID:[Polycythemia vera developed after a major molecular response to imatinib mesylate treatment in a patient with chronic myelogenous leukemia]. 2468 42

Myeloproliferative neoplasms (MPNs) are clonal disorders divided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) or Ph chromosome-negative MPNs. Co-occurrence of these disease entities is very rare and typically involves presence of common p190 or p210 BCR/ABL fusion transcript (responsible for CML) along with JAK2V617F mutation (most common driver mutation in Ph-negative MPNs). Because of the rarity of such cases, it is not clear if the outcomes are any different in these patients. In this article, we report a unique patient with polycythemia vera driven by a rare complex in-frame deletion-insertion mutation in JAK2 exon 12, and CML driven by uncommon p210 e14a3 (b3a3) BCR/ABL fusion transcript. We describe clinical and laboratory features, bone marrow pathology, treatment, and overall outcome.
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PMID:Unique Case of Myeloproliferative Neoplasm with Two Rare Clonal Abnormalities: Rare JAK2 Exon 12 Mutation and Rare e14a3 (b3a3) BCR/ABL Fusion Transcript. 3046 63