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

doi:10.1089/bio.2017.0079

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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	42-52
Number of pages	11
Journal	Biopreservation and Biobanking
Volume	16
Issue number	1
DOIs	https://doi.org/10.1089/bio.2017.0079
State	Published - Feb 2018

Keywords

AML
biomarkers
biorepository
cryopreservation
flow cytometry
immunophenotype

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
Cell Biology

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10.1089/bio.2017.0079

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Pogosova-Agadjanyan, E. L., Moseley, A., Othus, M., Appelbaum, F. R., Chauncey, T. R., Chen, I. M. L., Erba, H. P., Godwin, J. E., Fang, M., Kopecky, K. J., List, A. F., Pogosov, G. L., Radich, J. P., Willman, C. L., Wood, B. L., Meshinchi, S., & Stirewalt, D. L. (2018). Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report. Biopreservation and Biobanking, 16(1), 42-52. https://doi.org/10.1089/bio.2017.0079

Pogosova-Agadjanyan, EL, Moseley, A, Othus, M, Appelbaum, FR, Chauncey, TR, Chen, IML, Erba, HP, Godwin, JE, Fang, M, Kopecky, KJ, List, AF, Pogosov, GL, Radich, JP, Willman, CL, Wood, BL, Meshinchi, S & Stirewalt, DL 2018, 'Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report', Biopreservation and Biobanking, vol. 16, no. 1, pp. 42-52. https://doi.org/10.1089/bio.2017.0079

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

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",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2018, Mary Ann Liebert, Inc.",

year = "2018",

month = feb,

doi = "10.1089/bio.2017.0079",

language = "English (US)",

volume = "16",

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T1 - Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia

T2 - A SWOG Report

AU - Pogosova-Agadjanyan, Era L.

AU - Moseley, Anna

AU - Othus, Megan

AU - Appelbaum, Frederick R.

AU - Chauncey, Thomas R.

AU - Chen, I. Ming L.

AU - Erba, Harry P.

AU - Godwin, John E.

AU - Fang, Min

AU - Kopecky, Kenneth J.

AU - List, Alan F.

AU - Pogosov, Galina L.

AU - Radich, Jerald P.

AU - Willman, Cheryl L.

AU - Wood, Brent L.

AU - Meshinchi, Soheil

AU - Stirewalt, Derek L.

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

KW - AML

KW - biomarkers

KW - biorepository

KW - cryopreservation

KW - flow cytometry

KW - immunophenotype

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SN - 1947-5535

VL - 16

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EP - 52

JO - Biopreservation and Biobanking

JF - Biopreservation and Biobanking

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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