title: Cytoplasmic mutated nucleophosmin is stable in primary leukemic cells and in a xenotransplant model of NPMc+ acute myeloid leukemia in SCID mice.
abstract: We investigated the NPM1 mutation status or subcellular expression of NPM protein (nuclear vs. aberrant cytoplasmic) at diagnosis and relapse in 125 patients with acute myeloid leukemia from Italy and Germany. All 52 patients with acute myeloidleukemia carrying at diagnosis mutated or cytoplasmic NPM (NPMc(+) acute myeloid leukemia) retained this feature at relapse. Notably, cytoplasmic mutated NPM has now been retained for eight years in a xenotransplant model of NPMc(+) acute myeloid leukemia in immunodeficient mice. None of 73 acute myeloid leukemia patients carrying at diagnosis wild-type NPM1 gene or showing at immunohistochemistry nucleus-restricted expression of nucleophosmin (NPMc(-) acute myeloid leukemia), which is predictive of NPM1 gene in germline configuration, acquired cytoplasmic mutated NPM at relapse. This finding further confirms that NPMc(+) acute myeloid leukemia represents a primary event rather than a transformation stage of NPMc(-) acute myeloid leukemia. The stability of cytoplasmic mutated NPM in patients with acute myeloid leukemia, even at relapse in extramedullary sites, and in a xenotransplant model, suggest this event is crucial for leukemogenesis and represents the rationale for monitoring minimal residual disease and molecular targeted therapy in NPMc(+) acute myeloid leukemia.
authors: Institute of Hematology, University of Perugia, Perugia, Italy. faliniem@unipg.it
authors: Brunangelo
authors: B
authors: Falini
authors: Maria Paola
authors: MP
authors: Martelli
authors: Cristina
authors: C
authors: Mecucci
authors: Arcangelo
authors: A
authors: Liso
authors: Niccolò
authors: N
authors: Bolli
authors: Barbara
authors: B
authors: Bigerna
authors: Alessandra
authors: A
authors: Pucciarini
authors: Stefano
authors: S
authors: Pileri
authors: Giovanna
authors: G
authors: Meloni
authors: Massimo F
authors: MF
authors: Martelli
authors: Torsten
authors: T
authors: Haferlach
authors: Susanne
authors: S
authors: Schnittger
mesh_terms: D000328:Adult; D000818:Animals; D002869:Chromosome Aberrations; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D012008:Recurrence
chemical_list: C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D000090243:Nucleophosmin