Philadelphia, March 27, 2025 – Researchers have found that the clinical application of BCR::ABL1 digital PCR can reliably quantify stable deep molecular remission of chronic myeloid leukemia (CML), which will help to determine for which patients chronic drug treatment could potentially be discontinued. This transcript that is unique for CML is more sensitive and accurate than the current standard, real-time quantitative PCR (RT-qPCR), for detecting ultralow levels of residual leukemic disease. Results are reported in a novel study in The Journal of Molecular Diagnostics , published by Elsevier.
Lead investigator Peter E. Westerweel, MD, PhD, Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands, says, "In our research, we show that digital PCR for BCR::ABL reaches a sufficiently high sensitivity in almost all (97%) samples of patients in deep molecular remission. The molecular target was detected in two thirds of patients that were below the limit of detection of standard RT-qPCR technique. Digital PCR was therefore more sensitive and more accurate, allowing a reliable measurement to select CML patients in deep remission eligible for drug treatment discontinuation."
BCR::ABL1 is a specific genetic fusion protein that is characteristic of CML, which is created when two genes, BCR and ABL1, become abnormally joined together. With targeted therapy using tyrosine kinase inhibitors (TKIs), patients with CML may achieve deep molecular responses. Patients who reach this depth of remission can have a normal life expectancy and may qualify for a TKI discontinuation attempt.
In a nationwide prospective multicenter study, samples were collected from Dutch patients with CML for whom a TKI discontinuation attempt was under consideration. From July 2020, a total of 168 samples from 136 patients with CML from 31 medical centers were received until the time of analysis in May 2023.
Commenting on the findings of the study, Dr. Westerweel says, "BCR::ABL1 digital PCR was found to accurately quantify BCR::ABL1 around the level of 0.0023% on the International Scale, which is the clinically relevant prediction cutoff in the context of treatment-free remission. The target sensitivity was set at MR5.0, requiring reliable detection of one transcript in a background of at least 100,000 regular copies. This was achieved in 97% of assessments. Digital PCR was able to detect and quantify the BCR::ABL construct in 68% of samples below the limit of detection of current standard RT-qPCR."
In addition, researchers noted that there was a difference between patients in the fluorescence level of droplets rendered by the digital PCR technique. This was due to a difference in transcript type carried by individual patients. Droplets with higher fluorescence contain the target transcript type and are considered positive while droplets with low fluorescence are considered negative.
Dr. Westerweel explains, "Some patients have a so-called e13a2 transcript type, while others have an e14a2 transcript type. We validated that the assay can be used to identify the transcript type in patients with detectable disease. This additional discovery is very relevant as we have previously shown that the transcript type is a risk factor for molecular relapse after drug discontinuation. Often, the transcript type is not known for patients and cannot be established using standard techniques once patients are in deep remission."
Digital PCR for BCR::ABL in this study used an FDA-approved commercially available assay, which makes general use feasible. This technology may improve the management of CML by enabling more precise monitoring of minimal residual disease and better risk assessment for patients considering treatment-free remission.
Dr. Westerweel concludes, "Digital PCR for BCR::ABL is a valuable and reliable tool to aid clinical decision making in CML."
