title: The FLT3ITD mRNA level has a high prognostic impact in NPM1 mutated, but not in NPM1 unmutated, AML with a normal karyotype.
abstract: The impact of a FLT3-internal tandem duplication (FLT3ITD) on prognosis of patients with acute myeloid leukemia (AML) is dependent on the ratio of mutated to wild-type allele. In 648 normal karyotype (NK) AML patients, we found a significant independent effect of the quantitative FLT3ITD mRNA level--measured as (FLT3ITD/wtFLT3)/(FLT3ITD/wtFLT3+1)--on outcome. Moreover, this effect was clearly seen in 329 patients with a mutated NPM1 gene (NPM1+), but not in 319 patients without a NPM1 mutation (wtNPM1). In a multivariate Cox regression model, the quantitative FLT3ITD mRNA level showed an independent prognostic impact on overall survival (OS) and relapse-free survival (RFS) only in the NPM1+ subgroup (OS: hazard ratio, 5.9; [95% confidence interval [CI]: 3.1-11.2]; RFS: hazard ratio, 7.5 [95% CI: 3.4-16.5]). The FLT3ITD mRNA level contributes to relapse risk stratification and might help to guide postremission therapy in NPM1-mutated AML.
authors.affiliation: Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital Munich, and Institute of Medical Statistics, Biometry, and Epidemiology, University of Munich, 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: Evelyn
authors.initials: E
authors.lastname: Zellmeier
authors.forename: Purvi M
authors.initials: PM
authors.lastname: Kakadia
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: 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: Büchner
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Wörmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000502:physiology; D016019:Survival Analysis; D020080:Tandem Repeat Sequences / Q000235:genetics*; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000032:analysis / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3