title: Myeloproliferative neoplasms: Current molecular biology and genetics.
abstract: Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by increased production of mature blood cells. Philadelphia chromosome-negative MPNs (Ph-MPNs) consist of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). A number of stem cell derived mutations have been identified in the past 10 years. These findings showed that JAK2V617F, as a diagnostic marker involving JAK2 exon 14 with a high frequency, is the best molecular characterization of Ph-MPNs. Somatic mutations in an endoplasmic reticulum chaperone, named calreticulin (CALR), is the second most common mutation in patients with ET and PMF after JAK2 V617F mutation. Discovery of CALR mutations led to the increased molecular diagnostic of ET and PMF up to 90%. It has been shown that JAK2V617F is not the unique event in disease pathogenesis. Some other genes' location such as TET oncogene family member 2 (TET2), additional sex combs-like 1 (ASXL1), casitas B-lineage lymphoma proto-oncogene (CBL), isocitrate dehydrogenase 1/2 (IDH1/IDH2), IKAROS family zinc finger 1 (IKZF1), DNA methyltransferase 3A (DNMT3A), suppressor of cytokine signaling (SOCS), enhancer of zeste homolog 2 (EZH2), tumor protein p53 (TP53), runt-related transcription factor 1 (RUNX1) and high mobility group AT-hook 2 (HMGA2) have also identified to be involved in MPNs phenotypes. Here, current molecular biology and genetic mechanisms involved in MNPs with a focus on the aforementioned factors is presented.
authors.affiliation: Department of Medical Genetics, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: kolsoum.saeidi@gmail.com.
authors.forename: Kolsoum
authors.initials: K
authors.lastname: Saeidi
mesh_terms: D037282:Calreticulin / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics; D005091:Exons; D016158:Genes, p53; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics*
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; C000717967:DNMT3A protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D053628:Receptors, Thrombopoietin; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D050721:Proto-Oncogene Proteins c-cbl; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C067419:CBL protein, human
keywords: CALR; JAK2; Myeloproliferative neoplasms; Polycythemia vera