Validation of DNA methylation to predict outcome in acute myeloid leukemia by use of xMELP

Gerald B.W. Wertheim, Catherine Smith, Marlise Luskin, Alison Rager, Maria E. Figueroa, Martin Carroll, Stephen R. Master

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Epigenetic dysregulation involving alterations in DNA methylation is a hallmark of various types of cancer, including acute myeloid leukemia (AML). Although specific cancer types and clinical aggressiveness of tumors can be determined by DNA methylation status, the assessment of DNA methylation at multiple loci is not routinely performed in the clinical laboratory.

Methods: We recently described a novel microspherebased assay for multiplex evaluation of DNA methylation. In the current study, we validated and used an improved assay [termed expedited microsphere HpaII small fragment Enrichment by Ligationmediated PCR (xMELP)] that can be performed with appropriate clinical turnaround time.

Results: Using the xMELP assay in conjunction with a new 17-locus random forest classifier that has been trained using 344 AML samples, we were able to segregate an independent cohort of 70 primary AML patients into methylation-determined subgroups with significantly distinct mortality risk (P = 0.009). We also evaluated precision, QC parameters, and preanalytic variables of the xMELP assay and determined the sensitivity of the random forest classifier score to failure at 1 or more loci.

Conclusions: Our results demonstrate that xMELP performance is suitable for implementation in the clinical laboratory and predictsAMLoutcome in an independent patient cohort.

Original languageEnglish (US)
Pages (from-to)249-258
Number of pages10
JournalClinical chemistry
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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