title: BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.
abstract: BAALC and ERG expression levels are prognostic markers in younger (< 60 years) cytogenetically normal acute myeloid leukemia (CN-AML) adults; their prognostic impact in older (≥ 60 years) patients requires further investigation. We evaluated pretreatment expression of BAALC and ERG in 158 de novo patients treated on cytarabine/daunorubicin-based protocols. The patients were also characterized for other established molecular prognosticators. Low BAALC and ERG expression levels were associated with better outcome in univariable and multivariable analyses. Expression levels of both BAALC and ERG were the only factors significantly associated with overall survival upon multivariable analysis. To gain biological insights, we derived gene expression signatures associated with BAALC and ERG expression in older CN-AML patients. Furthermore, we derived the first microRNA expression signatures associated with the expression of these 2 genes. In low BAALC expressers, genes associated with undifferentiated hematopoietic precursors and unfavorable outcome predictors were down-regulated, whereas HOX genes and HOX-gene-embedded microRNAs were up-regulated. Low ERG expressers presented with down-regulation of genes involved in the DNA-methylation machinery, and up-regulation of miR-148a, which targets DNMT3B. We conclude that in older CN-AML patients, low BAALC and ERG expression associates with better outcome and distinct gene and microRNA expression signatures that could aid in identifying new targets and novel therapeutic strategies for older patients.
authors.affiliation: Department of Internal Medicine, 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: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Kelsi B
authors.initials: KB
authors.lastname: Holland
authors.forename: Dean
authors.initials: D
authors.lastname: Margeson
authors.forename: Heiko
authors.initials: H
authors.lastname: Becker
authors.forename: Susan P
authors.initials: SP
authors.lastname: Whitman
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Wu
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Carter
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Maria R
authors.initials: MR
authors.lastname: Baer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D003561:Cytarabine / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D016896:Treatment Outcome
chemical_list: C442828:BAALC protein, human; D014408:Biomarkers, Tumor; C072312:ERG protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D003561:Cytarabine; D003630:Daunorubicin