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

The classic BCR-ABL1-negative myeloproliferative neoplasm is an operational sub-category of MPNs that includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The JAK2V617F mutation is found in ~ 95% of PV and 50-60% of ET or PMF. In most of the remaining JAK2V617F- negative PV cases, JAK2 exon 12 mutations are present. Amongst the JAK2V617F-negative ET or PMF 5-10% of patients carry mutations in the MPL gene. Prior to 2013, there was no specific molecular marker described in the remaining 30-40% ET and PMF. In December 2013, two research groups independently reported mutations in the gene CALR found specifically in ET (67-71%) and PMF (56-88%) but not in PV. Initially CALR mutations were reported mutually exclusive with JAK2 or MPL. However, co-occurrence of CALR mutations with JAK2V617F has been reported recently in a few MPN cases. Many studies have reported important diagnostic and prognostic significance of CALR mutations in ET and PMF patients and CALR mutation screening has been proposed to be incorporated into WHO diagnostic criteria for MPN. It is suggestive in diagnostic workup of MPN that CALR mutations should not be studied in MPN patients who carry JAK2 or MPL mutations. However JAK2V617F and CALR positive patients might have a different phenotype and clinical course, distinct from the JAK2-positive or CALR-positive subgroups and identification of the true frequency of these patients may be an important factor for defining the prognosis, risk factors and outcomes for MPN patients.
Asian Pac J Cancer Prev 2016
PMID:Coexisting JAK2V617F and CALR Exon 9 Mutations in Myeloproliferative Neoplasms - Do They Designate a New Subtype? 2703 13

PIZZ alpha-1 antitrypsin deficiency (AATD) is an autosomal recessive disease affecting approximately 100,000 individuals in the United States and one of the most common hereditary causes of liver disease.1 The most common form of the disease results from a single base pair mutation (Glu342Lys), known as the "Z" mutation, that encodes a mutant protein (Z alpha-1 antritypsin [AAT]) that is prone to misfolding and is retained in the endoplasmic reticulum (ER) rather than appropriately secreted. Some of the retained mutant protein attains an unusual aggregated or polymerized conformation. Retained polymeric ZAAT aggregates are hepatotoxic and lead to downstream liver disease in a subset of PiZZ neonates and adults through a gain-of-function mechanism. PiZZ individuals are likewise highly predisposed to developing chronic obstructive pulmonary disease (COPD)/emphysema as a result of low circulating levels of AAT protein and associated protease-antiprotease imbalance. Much of our understanding of the molecular pathogenesis of AATD is based on studies employing either transgenic mice that express the mutant human Z allele or immortalized cell lines transduced to overexpress ZAAT. While they have been quite informative, these models fail to capture the patient-to-patient variability in disease phenotype that clinicians observe in their AATD patients, raising the question of whether alternative models might provide new insight. Induced pluripotent stem cells (iPSCs), first described in 2006, have the capacity to differentiate into a broad array of cell types from all 3 germ layers, including hepatocytes. Disease-specific iPSCs have been derived from patients with a variety of monogenic disorders and have been found to faithfully recapitulate features of such diseases as spinal muscular atrophy, familial dysautonomia, Rett syndrome, polycythemia vera, type 1A glycogen storage disease, familial hypercholesterolemia, long QT syndrome, and others. This discussion reviews the potential applications of iPSCs for understanding AATD-associated liver disease as well as for development of potential therapeutic strategies.
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PMID:Patient-Derived Induced Pluripotent Stem Cells for Alpha-1 Antitrypsin Deficiency Disease Modeling and Therapeutic Discovery. 3072 83