A new personalized DNA-based digital polymerase chain reaction (dPCR) assay could help determine which patients with chronic myeloid leukemia (CML) are more likely to relapse while in molecular remission.
Advances in CML treatment have led to significant improvements in the survival of patients with the disease. About 40% of patients who achieve sustained undetectable levels of the hybrid gene BCR-ABL1 in the blood or bone marrow remain disease-free even after treatment has been discontinued. However, CML reoccurs in the other 60% of patients, indicating a need for more sensitive methods of detecting which patients are most likely to relapse.
Currently, DNA-based quantitative-PCR (qPCR) is the most common method of testing for BCR-ABL1. In a study published in The Journal of Molecular Diagnostics, investigators sought to validate a more sensitive, personalized DNA-based dPCR approach for detecting low levels of residual CML in comparison with reverse transcriptase-digital PCR (RT-dPCR), reverse transcriptase-quantitative PCR (RT-qPCR), and qPCR approaches.
A total of 36 samples from 6 patients with early CML in molecular remission were analyzed in the study. The dPCR method was shown to be the most effective for detecting persistent disease: the BCR-ABL1 biomarker was identified in 81% of the samples, compared with only 25% and 19% for RT-dPCR and qPCR, respectively.
The dPCR approach involves identification of translocation t(9;22) fusion junctions using targeted next-generation sequencing. These genetic breakpoints, which vary in number and location between patients, then can be used to design patient-specific assays for the BCR-ABL1 hybrid gene, which is a product of the translocation.
Lead investigator of the study, Jane F Apperley, MD, PhD, FRCPath, of the Centre for Haematology, Imperial College, London, UK, explained that dPCR testing could dramatically impact how CML is managed by allowing for more informed decisions about whether to discontinue treatment for patients in molecular remission. “The technique we describe, with which we successfully mapped a disease-specific junction in all patients tested, is relatively simple, cost effective, and suited to a high-throughput laboratory," explained Dr. Apperley.
