title: Amount of bone marrow blasts is strongly correlated to NPM1 and FLT3-ITD mutation rate in AML with normal karyotype.
abstract: FLT3-ITDs are linked to higher leukocytes/blasts in acute myeloid leukemia. To evaluate the effect of NPM1 mutations, we correlated NPM1mut status with morphology in 805 adult normal karyotype AML. NPM1mut were found in 391/805 (48.6%), FLT3-ITD in 219/805 (27.2%). Frequencies of FLT3-ITD and NPM1mut cases were continuously increasing by blast decades: NPM1mut from 38/123 (30.9%) in 20-29% blast decade to 70/103 (68.0%) in 90-100% decade (p<0.001), FLT3-ITDs from 15/123 (12.2%) to 58/103 (56.3%) (p<0.001). Mean WBC count was highest in NPM1-mut/FLT3-ITD-positive and lowest in NPM1-wildtype/FLT3-ITD-negative patients (p<0.0001); similar for BM blasts. Therefore, FLT3-ITD and NPM1mut might synergistically stimulate blast proliferation.
authors.affiliation: MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany. torsten.haferlach@mll.com
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000235:genetics; D001854:Bone Marrow Cells / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D020440:Gene Duplication; D056726:Genetic Association Studies; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D059645:Mutation Rate; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D020080:Tandem Repeat Sequences / Q000235:genetics; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3