Phosphatase of Regenerating Liver-3 (PRL-3) is associated with the progression and spread of cancer,…
Acute Lymphoblastic Leukemia (ALL) is a common type of cancer primarily affecting children. Unfortunately, patients who experience a relapse of ALL tend to have a poor prognosis. Detecting any remaining cancer cells, called minimal residual disease (MRD), and identifying its spread to the central nervous system (CNS), are crucial factors for predicting the disease’s outcome. Current methods of detecting MRD and CNS involvement rely on finding cancer cells in patient samples, which can be challenging.
In our new paper, we have developed a new approach that shows promise in assessing the cancer burden in ALL. We discovered that small fragments of DNA, called cell-free DNA (cfDNA), which are released by cancer cells into the body fluids of patients, can serve as a sensitive biomarker for evaluating the presence of ALL in the blood and CNS. Up until now, analysis of cfDNA has not been applied to ALL.
We developed a fast and simple detection method using Nanopore MinION sequencing to analyze cfDNA from samples from patients with B-cell ALL (B-ALL). We sequenced a specific gene arrangement in the cells called the IGH locus, unique to B cells. By quantifying the variations of IGH sequences in cfDNA, we could detect different cancer cell clones within the ALL and monitor their response to treatment. We identified the presence of cancer cells even when standard cell-count thresholds used to diagnose MRD in the clinic were not met.
Our findings suggest that cfDNA analysis could be a valuable tool for detecting the presence of ALL in patients, even when cancer cells are not physically present in the samples. The workflow we developed offers a straightforward, fast, and cost-effective assay that could complement the traditional diagnostic approaches for ALL. This new approach can potentially improve monitoring and treatment strategies for children with ALL.