title: miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia.
abstract: High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, 300 West 10th Ave, Columbus, OH 43210, USA.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Eisfeld
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schwind
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Deedra
authors.initials: D
authors.lastname: Nicolet
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: Jason H
authors.initials: JH
authors.lastname: Mendler
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Sandya
authors.initials: S
authors.lastname: Liyanarachchi
authors.forename: Ravi
authors.initials: R
authors.lastname: Patel
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Carter
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Tanner
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics
chemical_list: C442828:BAALC protein, human; D044783:F-Box Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C513808:USP40 protein, human; D043222:Ubiquitin Thiolesterase