title: CD34 expression predicts an adverse outcome in patients with NPM1-positive acute myeloid leukemia.
abstract: Patients with acute myeloid leukemia (AML) harboring an NPM1 mutation exhibit a heterogeneous clinical outcome. Recent studies have shown that the absence of FLT3 internal tandem duplication (FLT3-ITD) mutation confers a favorable prognosis in NPM1-positive AML. However, the prognostic impact of immunophenotypes in this subgroup remains unclear. In this study, FLT3 mutation status and immunophenotypic profile of 85 NPM1-positive patients with de novo AML were retrospectively analyzed and correlated with their clinical features and survival outcomes. Univariate analysis detected 5 markers with prognostic relevance: older age (≥60 years), high white blood cell (WBC) count (>30 × 10(9)/L), FLT3-ITD, CD7, and CD34 expression. Multivariate analysis showed that high WBC count was the only independent predictor of a lower complete remission rate (P = .019). Older age (P = .035), high WBC count (P = .008), FLT3-ITD (P = .012), and CD34 expression (P = .006) were independent predictors of a shorter event-free survival (EFS). High WBC count (P = .014), FLT3-ITD (P = .005), and CD34 expression (P = .047) were independent predictors of a shorter overall survival (OS). Furthermore, based on FLT3-ITD status in NPM1 mutation-positive patients, we showed that both high WBC and CD34 expression conferred a poor EFS (P = .010 and P = .016, respectively) and OS (P = .032 and P = .001, respectively) in the FLT3-ITD-negative group, whereas high WBC predicted a poor EFS (P = .016) and OS (P = .027) in the FLT3-ITD-positive group. Our results confirm the prognostic value of assessing FLT3-ITD mutations in NPM1-positive AML and identify the adverse prognostic impact of high WBC and CD34 expression in this subgroup of AML.
authors.affiliation: Department of Laboratory Hematology, University Health Network, Toronto, Ontario, Canada M5G 2C4; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A1.
authors.forename: Harry
authors.initials: H
authors.lastname: Dang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Joseph
authors.initials: J
authors.lastname: Brandwein
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells; D002170:Canada / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D007958:Leukocyte Count; D007964:Leukocytosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; FLT3-ITD; Immunophenotyping; NPM1; Prognosis