Performance Evaluation of the QXDx <i>BCR-ABL</i> %IS Droplet Digital PCR Assay

Chung, Hee Jung; Hur, Mina; Yoon, Seok-Nam; Hwang, Ki Won; Lim, Hwan Sub; Kim, Hyeong-Su; Moon, Hee‐Jong; Yun, Yeo‐Min

doi:10.3343/alm.2020.40.1.72

Cited by 35 publications

(33 citation statements)

References 12 publications

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“…It should be noted that ddPCR is already being used to detect pathogens, viruses, copy number variations, and rare mutations 25 . Furthermore, the Food and Drug Administration (FDA) has recently approved the use of ddPCR for monitoring the response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment 26 . In future studies, it will be critical to test whether the RNA mutation-based A3A assay is sensitive enough to detect A3A activity in different types of tumor samples from cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots

et al. 2020

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APOBEC3A is a cytidine deaminase driving mutagenesis, DNA replication stress and DNA damage in cancer cells. While the APOBEC3A-induced vulnerability of cancers offers an opportunity for therapy, APOBEC3A protein and mRNA are difficult to quantify in tumors due to their low abundance. Here, we describe a quantitative and sensitive assay to measure the ongoing activity of APOBEC3A in tumors. Using hotspot RNA mutations identified from APOBEC3A-positive tumors and droplet digital PCR, we develop an assay to quantify the RNA-editing activity of APOBEC3A. This assay is superior to APOBEC3A protein-and mRNA-based assays in predicting the activity of APOBEC3A on DNA. Importantly, we demonstrate that the RNA mutation-based APOBEC3A assay is applicable to clinical samples from cancer patients. Our study presents a strategy to follow the dysregulation of APOBEC3A in tumors, providing opportunities to investigate the role of APOBEC3A in tumor evolution and to target the APOBEC3A-induced vulnerability in therapy.

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Section: Discussionmentioning

confidence: 99%

Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots

et al. 2020

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“…79 However, digital PCR may become an important complement to qRT-PCR in decisions for attempting TFR, in particular, using a ddPCR method that reports BCR-ABL1 values on the IS. 86 Factors other than the depth of BCR-ABL1 response at the time of stopping TKI may influence sustained TFR. The duration of DMR before stopping treatment and longer duration of therapy were factors in the EURO-SKI study, which is the largest discontinuation trial.…”

Section: Does Real-time Quantitative Polymerase Chain Reaction Analysmentioning

confidence: 99%

Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?

Branford

2020

haematol

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The primary goal of tyrosine kinase inhibitor (TKI) therapy for patients with chronic myeloid leukemia is survival, which is achieved by the vast majority of patients. The initial response to therapy provides a sensitive measure of future clinical outcome. Measurement of BCR-ABL1 transcript levels using real-time quantitative polymerase chain reaction standardized to the international reporting scale is now the principal recommended monitoring strategy. The method is used to assess early milestone responses and provides a guide for therapeutic intervention. When patients successfully traverse the critical first 12 months of TKI therapy, most will head towards another milestone response, deep molecular response (DMR, BCR-ABL1 ≤0.01%). DMR is essential for patients aiming to achieve treatment-free remission and a prerequisite for a trial of TKI discontinuation. The success of discontinuation trials has led to new treatment strategies in order for more patients to reach this milestone response. DMR has been incorporated into endpoints of clinical trials and is considered by some expert groups as the optimal treatment response. But is DMR a stable response and does it provide the ultimate protection against TKI resistance and death? Do we need to increase the sensitivity of detection of BCR-ABL1 to better identify the patients who would likely remain in treatment-free remission after TKI discontinuation? Is it necessary to switch current TKI therapy to a more potent inhibitor if the goal is to achieve DMR? These are issues that I will explore in this review.

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“…In addition, no outliers and no false-positive results were observed using QXDx BCR-ABL %IS ddPCR assay. They then suggested that this ddPCR kit could be a reliable and promising tool for MRD monitoring in CML patients [49].…”

Section: Dpcr To Monitor Bcr-abl1mentioning

confidence: 99%

Standardization of BCR-ABL1 p210 Monitoring: From Nested to Digital PCR

Jovanovski

Petiti

Gatto

et al. 2020

Cancers

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The introduction of tyrosine kinase inhibitors in 2001 as a targeted anticancer therapy has significantly improved the quality of life and survival of patients with chronic myeloid leukemia. At the same time, with the introduction of tyrosine kinase inhibitors, the need for precise monitoring of the molecular response to therapy has emerged. Starting with a qualitative polymerase chain reaction, followed by the introduction of a quantitative polymerase chain reaction to determine the exact quantity of the transcript of interest-p210 BCR-ABL1, molecular monitoring in patients with chronic myeloid leukemia was internationally standardized. This enabled precise monitoring of the therapeutic response, unification of therapeutic protocols, and comparison of results between different laboratories. This review aims to summarize the steps in the diagnosis and molecular monitoring of p210 BCR-ABL1, as well as to consider the possible future application of a more sophisticated method such as digital polymerase chain reaction.

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Performance Evaluation of the QXDx BCR-ABL %IS Droplet Digital PCR Assay

Cited by 35 publications

References 12 publications

Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots

Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots

Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?

Standardization of BCR-ABL1 p210 Monitoring: From Nested to Digital PCR

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