title: NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS).
abstract: Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in NPM1(+) (75% and 80%, respectively) than in NPM1(-) (57% and 57%, respectively) patients, but were unaffected by the FLT3-ITD status. Multivariate analyses revealed the presence of a NPM1 mutation as an independent positive prognostic factor for the achievement of an adequate day-16 blast clearance and a CR. In conclusion, NPM1(+) blast cells show a high in vivo sensitivity toward induction chemotherapy irrespective of the FLT3-ITD mutation status. These findings provide insight into the pathophysiology and help to understand the favorable clinical outcome of patients with NPM1(+) AML.
authors.affiliation: Department of Medicine III, University Hospital Munich, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Schneider
authors.forename: Eva
authors.initials: E
authors.lastname: Hoster
authors.forename: Michael
authors.initials: M
authors.lastname: Unterhalt
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schneider
authors.forename: Annika
authors.initials: A
authors.lastname: Dufour
authors.forename: Tobias
authors.initials: T
authors.lastname: Benthaus
authors.forename: Gudrun
authors.initials: G
authors.lastname: Mellert
authors.forename: Evelin
authors.initials: E
authors.lastname: Zellmeier
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
authors.forename: Michaela
authors.initials: M
authors.lastname: Feuring-Buske
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
authors.forename: Jan
authors.initials: J
authors.lastname: Braess
authors.forename: Susanne
authors.initials: S
authors.lastname: Fritsch
authors.forename: Achim
authors.initials: A
authors.lastname: Heinecke
authors.forename: Maria C
authors.initials: MC
authors.lastname: Sauerland
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Thomas
authors.initials: T
authors.lastname: Buechner
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Woermann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D055029:Inverted Repeat Sequences; D007621:Karyotyping; D007694:Killer Cells, Natural; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012074:Remission Induction; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3