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首页> 外文期刊>Biopreservation and biobanking >Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report
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Impact of Specimen Heterogeneity on Biomarkers in Repository Samples from Patients with Acute Myeloid Leukemia: A SWOG Report

机译:急性髓性白血病患者储存库样品中标本异质性对生物标志物的影响:播种报告

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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.
机译:简介:急性髓性白血病(AML)的目前预后模型在预测个别患者的临床结果时不一致。用于生物标志物发现和验证的标本质量的可变性可能导致这种预后不一致。方法:我们评估了样品异质性对预后生物标志物的影响和减轻来自血腥患者的240乳髓和外周血标本中这种异质性的任何不良反应的方法。结果:冷冻保存样品在活力(带有寿命≤60%的37%)和非全血症细胞污染(带淋巴细胞百分比> 20%)的宽范围(37%)显示出广泛的可行性(37%)。标本活力受到运输时间,AML免疫表型,并且可能是患者年龄的影响。未溺食样品中的活力和细胞异质性显着改变了生物标志物结果。富集可行的AML爆炸改善了具有差的可活力和RNA和RNA生物标志物的差异的标本的RNA质量。例如,FLT3 -ITD的等位基因比对于风险危害AML患者的等位基因比在可行的AML爆炸中平均为1.49倍,而不是未侵入的标本。结论:据我们所知,这是第一次提供证据表明,使用冷冻保存的标本可以引入可能影响生物标志物的无法控制的变量,并为可行的AML爆炸进行富集可能会降低这种影响。

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