title: A patient with a 20-year lag phase between JAK2-V617F+ myeloproliferation and NPM1-mutated AML arguing against a common origin of disease.
abstract: We have sought to unravel the molecular biology of a female patient who in 1985 at the age of 55 was diagnosed with a chronic myeloproliferative neoplasm (MPN) and in whom overt acute myeloid leukemia (AML) developed in 2005. To this end, DNA and RNA (extracted from either paraffin-embedded bone marrow (BM) or from BM and/or peripheral blood stored in an RNA/DNA-preserving buffer) were analyzed by qPCR and by capillary gel electrophoresis of PCR products. We found the patient to be JAK2-V617F mutation positive throughout the course of disease, while a mutation of the nucleophosmin (NPM1) gene emerged at AML diagnosis and relapse. The 20-yr lag phase between the polycythemia vera and the AML adds indirect evidence to the growing realization that the leukemic transformation in patients with MPN occurs from in a JAK2 wild-type stem cell.
authors.affiliation: Department of Hematology, Aarhus University Hospital, Tage-Hansens Gade 2, Aarhus C, Denmark. roug@ki.au.dk
authors.forename: Anne Stidsholt
authors.initials: AS
authors.lastname: Roug
authors.forename: Charlotte Guldborg
authors.initials: CG
authors.lastname: Nyvold
authors.forename: Caroline
authors.initials: C
authors.lastname: Juhl-Christensen
authors.forename: Mariann
authors.initials: M
authors.lastname: Christensen
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Peter
authors.initials: P
authors.lastname: Hokland
mesh_terms: D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D053614:Janus Kinase 2