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Biopreserv Biobank. 2018 Feb;16(1):42-52. doi: 10.1089/bio.2017.0079. Epub 2017 Nov 27.

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

Author information

1
1 Clinical Research Division , Fred Hutch, Seattle, Washington.
2
2 SWOG Statistical Center , Fred Hutch, Seattle, Washington.
3
3 Departments of Oncology and Hematology, University of Washington , Seattle, Washington.
4
4 VA Puget Sound Health Care System , Seattle, Washington.
5
5 Department of Pathology, University of New Mexico , UNM Comprehensive Cancer Center, Albuquerque, New Mexico .
6
6 Division of Hematology and Oncology, University of Alabama at Birmingham , Birmingham, Alabama.
7
7 Providence Cancer Center, Earle A. Chiles Research Institute , Portland, Oregon.
8
8 Departments of Laboratory Medicine and Pathology, University of Washington , Seattle, Washington.
9
9 Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, Florida.
10
10 Department of Pediatrics, University of Washington , Seattle, Washington.

Abstract

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.

KEYWORDS:

AML; biomarkers; biorepository; cryopreservation; flow cytometry; immunophenotype

PMID:
29172682
PMCID:
PMC5808392
[Available on 2019-02-01]
DOI:
10.1089/bio.2017.0079
[Indexed for MEDLINE]

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