title: Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia.
abstract: Some studies have suggested that cases of acute myeloid leukemia (AML) with low levels of FLT3 internal tandem duplications (FLT3(ITD)) do not have a worse prognosis if there is a concomitant NPM1 mutation, although this is controversial. To clarify this therapeutically important issue, we have analyzed FLT3(ITD) and NPM1(MUT) levels in 1609 younger adult cases of cytogenetically intermediate-risk AML. The cumulative incidence of relapse was increased in NPM1(MUT) cases by the presence of a FLT3(ITD), but did not differ markedly according to FLT3(ITD) level. This remained true when allowance was made for poor leukemic cell purity by adjustment of the FLT3(ITD) level to the measured NPM1(MUT) level. If consolidation therapies are to be determined by relapse risk, then NPM1(MUT) cases with low-level FLT3(ITD) should not be considered as good risk without further studies. AML 12 and AML 15 are registered at http://www.controlled-trials.com under ISRCTN17833622 and ISRCTN17161961, respectively.
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom; and.
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.affiliation: Department of Haematology, Cardiff University School of Medicine, Cardiff, United Kingdom.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom; and.
authors.forename: Asim
authors.initials: A
authors.lastname: Khwaja
authors.affiliation: Department of Haematology, University College London Cancer Institute, London, United Kingdom; and.
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Gale
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D018628:Gene Dosage; D020440:Gene Duplication; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D018598:Minisatellite Repeats; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D012008:Recurrence; D012306:Risk; D016019:Survival Analysis; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3