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

Publication ,  Journal Article
Pogosova-Agadjanyan, EL; Moseley, A; Othus, M; Appelbaum, FR; Chauncey, TR; Chen, I-ML; Erba, HP; Godwin, JE; Fang, M; Kopecky, KJ; List, AF ...
Published in: Biopreserv Biobank
February 2018

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.

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Published In

Biopreserv Biobank

DOI

EISSN

1947-5543

Publication Date

February 2018

Volume

16

Issue

1

Start / End Page

42 / 52

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Specimen Handling
  • RNA, Neoplasm
  • Male
  • Leukemia, Myeloid, Acute
  • Immunophenotyping
  • Humans
  • Female
  • DNA, Neoplasm
  • Cryopreservation
 

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Pogosova-Agadjanyan, E. L., Moseley, A., Othus, M., Appelbaum, F. R., Chauncey, T. R., Chen, I.-M., … Stirewalt, D. L. (2018). Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report. Biopreserv Biobank, 16(1), 42–52. https://doi.org/10.1089/bio.2017.0079
Pogosova-Agadjanyan, Era L., Anna Moseley, Megan Othus, Frederick R. Appelbaum, Thomas R. Chauncey, I-Ming L. Chen, Harry P. Erba, et al. “Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report.Biopreserv Biobank 16, no. 1 (February 2018): 42–52. https://doi.org/10.1089/bio.2017.0079.
Pogosova-Agadjanyan EL, Moseley A, Othus M, Appelbaum FR, Chauncey TR, Chen I-ML, et al. Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report. Biopreserv Biobank. 2018 Feb;16(1):42–52.
Pogosova-Agadjanyan, Era L., et al. “Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report.Biopreserv Biobank, vol. 16, no. 1, Feb. 2018, pp. 42–52. Pubmed, doi:10.1089/bio.2017.0079.
Pogosova-Agadjanyan EL, Moseley A, Othus M, Appelbaum FR, Chauncey TR, Chen I-ML, Erba HP, Godwin JE, Fang M, Kopecky KJ, List AF, Pogosov GL, Radich JP, Willman CL, Wood BL, Meshinchi S, Stirewalt DL. Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report. Biopreserv Biobank. 2018 Feb;16(1):42–52.
Journal cover image

Published In

Biopreserv Biobank

DOI

EISSN

1947-5543

Publication Date

February 2018

Volume

16

Issue

1

Start / End Page

42 / 52

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Specimen Handling
  • RNA, Neoplasm
  • Male
  • Leukemia, Myeloid, Acute
  • Immunophenotyping
  • Humans
  • Female
  • DNA, Neoplasm
  • Cryopreservation