TitleA clinical measure of DNA methylation predicts outcome in de novo acute myeloid leukemia.
Publication TypeJournal Article
Year of Publication2016
AuthorsLuskin, Marlise R., Gimotty Phyllis A., Smith Catherine, Loren Alison W., Figueroa Maria E., Harrison Jenna, Sun Zhuoxin, Tallman Martin S., Paietta Elisabeth M., Litzow Mark R., Melnick Ari M., Levine Ross L., Fernandez Hugo F., Luger Selina M., Carroll Martin, Master Stephen R., and Wertheim Gerald B. W.
JournalJCI Insight
Date Published2016 Jun 16

<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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).</p><p><b>RESULTS: </b>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 ( = 0.011) and failure to achieve CR ( = 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.</p><p><b>CONCLUSION: </b>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.</p>

Alternate JournalJCI Insight
PubMed ID27446991
PubMed Central IDPMC4951094
Grant ListI01 BX000918 / BX / BLRD VA / United States
U24 CA196172 / CA / NCI NIH HHS / United States
R01 CA149566 / CA / NCI NIH HHS / United States
UL1 TR000003 / TR / NCATS NIH HHS / United States
T32 CA009679 / CA / NCI NIH HHS / United States
P30 CA016520 / CA / NCI NIH HHS / United States
U10 CA180820 / CA / NCI NIH HHS / United States
U10 CA180794 / CA / NCI NIH HHS / United States
R21 CA185365 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U10 CA180791 / CA / NCI NIH HHS / United States