Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report

Era L. Pogosova-Agadjanyan, Anna Moseley, Megan Othus, Frederick R. Appelbaum, Thomas R. Chauncey, I. Ming L. Chen, Harry P. Erba, John E. Godwin, Min Fang, Kenneth J. Kopecky, Alan F. List, Galina L. Pogosov, Jerald P. Radich, Cheryl L. Willman, Brent L. Wood, Soheil Meshinchi, Derek L. Stirewalt

Research output: Contribution to journalArticlepeer-review


Introduction: Current prognostic models for acute myeloid leukemia (AML) are inconsistent at predicting clinical outcomes for individual patients. Variability in the quality of specimens utilized for biomarker discovery and validation may contribute to this prognostic inconsistency. Methods: We evaluated the impact of sample heterogeneity on prognostic biomarkers and methods to mitigate any adverse effects of this heterogeneity in 240 cryopreserved bone marrow and peripheral blood specimens from AML patients enrolled on SWOG (Southwest Oncology Group) trials. Results: Cryopreserved samples displayed a broad range in viability (37% with viabilities ≤60%) and nonleukemic cell contamination (13% with lymphocyte percentages >20%). Specimen viability was impacted by transport time, AML immunophenotype, and, potentially, patients' age. The viability and cellular heterogeneity in unsorted samples significantly altered biomarker results. Enriching for viable AML blasts improved the RNA quality from specimens with poor viability and refined results for both DNA and RNA biomarkers. For example, FLT3-ITD allelic ratio, which is currently utilized to risk-stratify AML patients, was on average 1.49-fold higher in the viable AML blasts than in the unsorted specimens. Conclusion: To our knowledge, this is the first study to provide evidence that using cryopreserved specimens can introduce uncontrollable variables that may impact biomarker results and enrichment for viable AML blasts may mitigate this impact.

Original languageEnglish (US)
Pages (from-to)42-52
Number of pages11
JournalBiopreservation and Biobanking
Issue number1
StatePublished - Feb 2018


  • AML
  • biomarkers
  • biorepository
  • cryopreservation
  • flow cytometry
  • immunophenotype

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology


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