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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.

Publication ,  Journal Article
Schwind, S; Marcucci, G; Maharry, K; Radmacher, MD; Mrózek, K; Holland, KB; Margeson, D; Becker, H; Whitman, SP; Wu, Y-Z; Metzeler, KH ...
Published in: Blood
December 16, 2010

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.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 16, 2010

Volume

116

Issue

25

Start / End Page

5660 / 5669

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Transcriptional Regulator ERG
  • Trans-Activators
  • Survival Rate
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Proteins
  • Middle Aged
  • MicroRNAs
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schwind, S., Marcucci, G., Maharry, K., Radmacher, M. D., Mrózek, K., Holland, K. B., … Bloomfield, C. D. (2010). 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. Blood, 116(25), 5660–5669. https://doi.org/10.1182/blood-2010-06-290536
Schwind, Sebastian, Guido Marcucci, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Kelsi B. Holland, Dean Margeson, et al. “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.Blood 116, no. 25 (December 16, 2010): 5660–69. https://doi.org/10.1182/blood-2010-06-290536.
Schwind S, Marcucci G, Maharry K, Radmacher MD, Mrózek K, Holland KB, Margeson D, Becker H, Whitman SP, Wu Y-Z, Metzeler KH, Powell BL, Kolitz JE, Carter TH, Moore JO, Baer MR, Carroll AJ, Caligiuri MA, Larson RA, Bloomfield CD. 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. Blood. 2010 Dec 16;116(25):5660–5669.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

December 16, 2010

Volume

116

Issue

25

Start / End Page

5660 / 5669

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Transcriptional Regulator ERG
  • Trans-Activators
  • Survival Rate
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Proteins
  • Middle Aged
  • MicroRNAs