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JCI Insight. 2016 Jun 16;1(9). doi: 10.1172/jci.insight.87323.

A clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia.

JCI insight

Marlise R Luskin, Phyllis A Gimotty, Catherine Smith, Alison W Loren, Maria E Figueroa, Jenna Harrison, Zhuoxin Sun, Martin S Tallman, Elisabeth M Paietta, Mark R Litzow, Ari M Melnick, Ross L Levine, Hugo F Fernandez, Selina M Luger, Martin Carroll, Stephen R Master, Gerald B W Wertheim

Affiliations

  1. Division of Hematology and Oncology, Abramson Cancer Center at the University of Pennsylvania (UPENN), Philadelphia, Pennsylvania, USA.
  2. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania (UPENN), Philadelphia, Pennsylvania, USA.
  3. Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  4. University of Michigan Medical School, Ann Arbor, Michigan, USA.
  5. Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  6. Memorial Sloan Kettering Cancer Center, New York, New York, USA.
  7. Montefiore Medical Center, New York, New York, USA.
  8. Mayo Clinic, Rochester, Minnesota, USA.
  9. Hematology and Oncology Division, Weill Cornell Medical College, New York, New York, USA.
  10. Moffit Cancer Center, Tampa, Florida, USA.
  11. Division of Hematology and Oncology, Abramson Cancer Center at the University of Pennsylvania (UPENN), Philadelphia, Pennsylvania, USA; Philadelphia Veterans Administration Medical Center, Philadelphia, Pennsylvania, USA.
  12. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.
  13. Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

PMID: 27446991 PMCID: PMC4951094 DOI: 10.1172/jci.insight.87323

Abstract

BACKGROUND: Variable response to chemotherapy in acute myeloid leukemia (AML) represents a major treatment challenge. Clinical and genetic features incompletely predict outcome. The value of clinical epigenetic assays for risk classification has not been extensively explored. We assess the prognostic implications of a clinical assay for multilocus DNA methylation on adult patients with de novo AML.

METHODS: We performed multilocus DNA methylation assessment using xMELP on samples and calculated a methylation statistic (M-score) for 166 patients from UPENN with de novo AML who received induction chemotherapy. The association of M-score with complete remission (CR) and overall survival (OS) was evaluated. The optimal M-score cut-point for identifying groups with differing survival was used to define a binary M-score classifier. This classifier was validated in an independent cohort of 383 patients from the Eastern Cooperative Oncology Group Trial 1900 (E1900; NCT00049517).

RESULTS: A higher mean M-score was associated with death and failure to achieve CR. Multivariable analysis confirmed that a higher M-score was associated with death (

CONCLUSION: The M-score represents a valid binary prognostic classifier for patients with de novo AML. The xMELP assay and associated M-score can be used for prognosis and should be further investigated for clinical decision making in AML patients.

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