title: Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia.
abstract: Low MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene-embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.
authors.affiliation: Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Jessica
authors.initials: J
authors.lastname: Kohlschmidt
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D015996:Survival Rate; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C506524:MN1 protein, human; C000716967:NPM1 protein, human; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D000090243:Nucleophosmin