title: Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.
abstract: The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with < 12% JAK2(V617F) allelic burden. Current WHO guidelines do not recommend further testing once JAK2(V617F) mutation is detected in MPNs. The findings, however, indicate that quantification of JAK2(V617F) allele burden may be clinically relevant in MPNs and in those with low allelic burden additional testing for JAK2 exon-12 and MPL exon-10 mutation should be pursued.
authors.affiliation: a Associated Regional University Pathologists (ARUP) Laboratories ;
authors.forename: Roberto H
authors.initials: RH
authors.lastname: Nussenzveig
authors.affiliation: a Associated Regional University Pathologists (ARUP) Laboratories ;
authors.forename: Ha T
authors.initials: HT
authors.lastname: Pham
authors.affiliation: a Associated Regional University Pathologists (ARUP) Laboratories ;|b Department of Pathology ;
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Perkins
authors.affiliation: a Associated Regional University Pathologists (ARUP) Laboratories ;|b Department of Pathology ;|c Division of Hematology, Department of Internal Medicine, School of Medicine , University of Utah , Salt Lake City , UT , USA.
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
authors.affiliation: a Associated Regional University Pathologists (ARUP) Laboratories ;|b Department of Pathology ;
authors.forename: Archana M
authors.initials: AM
authors.lastname: Agarwal
authors.affiliation: a Associated Regional University Pathologists (ARUP) Laboratories ;|b Department of Pathology ;
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salama
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005787:Gene Frequency; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Co-existing mutations; allelic burden; myeloproliferative neoplasms