title: Clonal heterogeneity in patients with cytogenetically normal acute myeloid leukemia with NPM1 mutations.
abstract: The nucleophosmin 1 (NPM1) gene is one of the most commonly mutated genes in acute myeloid leukemia (AML), occurring in approximately 60% of adult cytogenetically normal AML (CN-AML). To date, these mutations have only been detected in cells of the myeloid lineage, whereas the potential clonal involvement of the lymphoid lineage is controversial. In our study, NPM1 mutations were analyzed using the highly sensitive real-time quantitative polymerase chain reaction (RQ-PCR) method on fluorescence-activated cell-sorted (FACS) purified different circulating mature cell populations in patients with NPM1-mutated CN-AML. As expected, NPM1 mutations were found in myeloid blood cells, including CD14(+) monocytes and CD66b(+) granulocytes. However, we were also able to detect NPM1 mutations in CD19(+) B cells and CD3(-)14(-)16(+)56(+) natural killer (NK) cells, albeit at lower levels. Surprisingly, mutations were also detected in CD3(+) T cells from all analyzed patients. Our data demonstrate that NPM1-mutated CN-AML originates in an early stem cell with both lymphoid and myeloid differentiation potential.
authors.affiliation: Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic. ddvorak@fnbrno.cz
authors.forename: Dana
authors.initials: D
authors.lastname: Dvorakova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Racil
authors.forename: Marek
authors.initials: M
authors.lastname: Borsky
authors.forename: Blanka
authors.initials: B
authors.lastname: Robesova
authors.forename: Ivana
authors.initials: I
authors.lastname: Jeziskova
authors.forename: Filip
authors.initials: F
authors.lastname: Razga
authors.forename: Martina
authors.initials: M
authors.lastname: Lengerova
authors.forename: Jiri
authors.initials: J
authors.lastname: Mayer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018628:Gene Dosage; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D010641:Phenotype
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin