A clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia Journal Article
| Authors: | Luskin, M. R.; Gimotty, P. A.; Smith, C.; Loren, A. W.; Figueroa, M. E.; Harrison, J.; Sun, Z.; Tallman, M. S.; Paietta, E. M.; Litzow, M. R.; Melnick, A. M.; Levine, R. L.; Fernandez, H. F.; Luger, S. M.; Carroll, M.; Master, S. R.; Wertheim, G. B. W. |
| Article Title: | A clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia |
| 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 (P = 0.011) and failure to achieve CR (P = 0.034). Median survival was 26.6 months versus 10.6 months for low and high M-score groups. The ability of the M-score to perform as a classifier was confirmed in patients <= 60 years with intermediate cytogenetics and patients who achieved CR, as well as in the E1900 validation cohort. 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. |
| Keywords: | survival; epigenetics; resistance; impact; hypermethylation; intensive chemotherapy; older; tet2 function; mutations result |
| Journal Title: | JCI Insight |
| Volume: | 1 |
| Issue: | 9 |
| ISSN: | 2379-3708 |
| Publisher: | Amer Soc Clinical Investigation Inc |
| Date Published: | 2016-06-16 |
| Start Page: | e87323 |
| Language: | English |
| ACCESSION: | WOS:000387112700011 |
| DOI: | 10.1172/jci.insight.87323 |
| PROVIDER: | wos |
| PMCID: | PMC4951094 |
| PUBMED: | 27446991 |
| Notes: | Article -- Source: Wos |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work