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Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients.

Publication ,  Journal Article
Achille, NJ; Othus, M; Phelan, K; Zhang, S; Cooper, K; Godwin, JE; Appelbaum, FR; Radich, JP; Erba, HP; Nand, S; Zeleznik-Le, NJ
Published in: Leuk Res
March 2016

Treatment options for older patients with acute myeloid leukemia (AML) range from supportive care alone to full-dose chemotherapy. Identifying factors that predict response to therapy may help increase efficacy and avoid toxicity. The phase II SWOG S0703 study investigated the use of hydroxyurea and azacitidine with gemtuzumab ozogamicin in the elderly AML population and found survival rates similar to those expected with standard AML regimens, with less toxicity. As part of this study, global DNA methylation along with promoter DNA methylation and expression analysis of six candidate genes (CDKN2A, CDKN2B, HIC1, RARB, CDH1 and APAF1) were determined before and during therapy to investigate whether very early changes are prognostic for clinical response. Global DNA methylation was not associated with a clinical response. Samples after 3 or 4 days of treatment with azacitidine showed significantly decreased CDKN2A promoter DNA methylation in patients achieving complete remission (CR) compared to those who did not. Samples from day 7 of treatment showed significantly decreased RARB, CDKN2B and CDH1 promoter DNA methylation in responders compared to nonresponders. Gene-specific DNA methylation analysis of peripheral blood samples may help early identification of those older AML patients most likely to benefit from demethylating agent therapy.

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Published In

Leuk Res

DOI

EISSN

1873-5835

Publication Date

March 2016

Volume

42

Start / End Page

68 / 74

Location

England

Related Subject Headings

  • Treatment Outcome
  • Transcriptome
  • Risk Factors
  • Real-Time Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Prognosis
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Achille, N. J., Othus, M., Phelan, K., Zhang, S., Cooper, K., Godwin, J. E., … Zeleznik-Le, N. J. (2016). Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients. Leuk Res, 42, 68–74. https://doi.org/10.1016/j.leukres.2016.01.004
Achille, Nicholas J., Megan Othus, Kathleen Phelan, Shubin Zhang, Kathrine Cooper, John E. Godwin, Frederick R. Appelbaum, et al. “Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients.Leuk Res 42 (March 2016): 68–74. https://doi.org/10.1016/j.leukres.2016.01.004.
Achille NJ, Othus M, Phelan K, Zhang S, Cooper K, Godwin JE, et al. Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients. Leuk Res. 2016 Mar;42:68–74.
Achille, Nicholas J., et al. “Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients.Leuk Res, vol. 42, Mar. 2016, pp. 68–74. Pubmed, doi:10.1016/j.leukres.2016.01.004.
Achille NJ, Othus M, Phelan K, Zhang S, Cooper K, Godwin JE, Appelbaum FR, Radich JP, Erba HP, Nand S, Zeleznik-Le NJ. Association between early promoter-specific DNA methylation changes and outcome in older acute myeloid leukemia patients. Leuk Res. 2016 Mar;42:68–74.
Journal cover image

Published In

Leuk Res

DOI

EISSN

1873-5835

Publication Date

March 2016

Volume

42

Start / End Page

68 / 74

Location

England

Related Subject Headings

  • Treatment Outcome
  • Transcriptome
  • Risk Factors
  • Real-Time Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Prognosis
  • Middle Aged
  • Male
  • Leukemia, Myeloid, Acute
  • Immunology