Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report
| Autor: | Frederick R. Appelbaum, Jerald P. Radich, John E. Godwin, Era L. Pogosova-Agadjanyan, Min Fang, I-Ming L. Chen, Derek L. Stirewalt, Cheryl L. Willman, Alan F. List, Kenneth J. Kopecky, Harry P. Erba, Thomas R. Chauncey, Brent L. Wood, Megan Othus, Anna Moseley, Galina Pogosov, Soheil Meshinchi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Cell Survival Lymphocyte Medicine (miscellaneous) General Biochemistry Genetics and Molecular Biology Immunophenotyping Specimen Handling Flow cytometry 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases Internal medicine Tumor Cells Cultured Humans Medicine RNA Neoplasm Biomarker discovery Adverse effect Biological Specimen Banks Cryopreservation medicine.diagnostic_test business.industry Correction Myeloid leukemia DNA Neoplasm Cell Biology General Medicine Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Biomarker (medicine) Female Bone marrow business Biomarkers |
| Zdroj: | Biopreservation and Biobanking. 16:42-52 |
| ISSN: | 1947-5543 1947-5535 |
| DOI: | 10.1089/bio.2017.0079 |
| Popis: | 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.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.Cryopreserved samples displayed a broad range in viability (37% with viabilities ≤60%) and nonleukemic cell contamination (13% with lymphocyte percentages20%). 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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|