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.
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.
Schwind
Sebastian
S
Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Marcucci
Guido
G
Maharry
Kati
K
Radmacher
Michael D
MD
Mrózek
Krzysztof
K
Holland
Kelsi B
KB
Margeson
Dean
D
Becker
Heiko
H
Whitman
Susan P
SP
Wu
Yue-Zhong
YZ
Metzeler
Klaus H
KH
Powell
Bayard L
BL
Kolitz
Jonathan E
JE
Carter
Thomas H
TH
Moore
Joseph O
JO
Baer
Maria R
MR
Carroll
Andrew J
AJ
Caligiuri
Michael A
MA
Larson
Richard A
RA
Bloomfield
Clara D
CD
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
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