A novel CRISPR-based diagnostic tool developed by researchers at Dana-Farber Cancer Institute offers the potential for rapid and accurate detection of gene fusions in acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML). This innovation addresses critical gaps in timely precision diagnostics, particularly in resource-limited settings, and could significantly improve patient outcomes.
The diagnostic, described in a study published in Blood, utilizes the CRISPR-based SHERLOCK platform to identify specific RNA sequences indicative of gene fusions common in APL and CML. The test can be performed at the point of care, providing results within two hours with 100% accuracy in tests on patient samples. This rapid turnaround is a significant improvement over traditional molecular diagnostics, which can take days to weeks.
"It doesn't matter if you have highly effective treatment for a disease if you can't diagnose that disease," said senior author Coleman Lindsley, MD, PhD, Dana-Farber physician-scientist. "By developing rapid, accurate, point-of-care tests for cancer, we hope to improve outcomes by increasing accessibility and timeliness of diagnostic testing."
Impact on APL and CML Treatment
In APL, rapid diagnosis is crucial due to the high risk of fatal bleeding during the period between disease onset and treatment initiation. Treatment with all-trans retinoic acid (ATRA) can immediately reverse this bleeding risk. Studies show that when rapid molecular diagnostics are available, fewer than 10% of patients with a fusion gene die from the disease, compared to as many as 30% when diagnostics are delayed.
"Our test can be used at the point of care, so an emergency room physician could know within a couple of hours if this patient should receive this essential lifesaving drug," explained first author Rahul Vedula, MD, Dana-Farber physician-scientist.
For CML, while effective and inexpensive oral precision medications exist, access to diagnostics remains a barrier in resource-limited countries. This new diagnostic could enable more patients to receive appropriate treatment.
Technology and Testing
The diagnostic searches for specific RNA sequences within blood samples, targeting two known alterations in each disease. The CRISPR mechanism ensures high accuracy by matching only with an exactly matched RNA code. The test accurately identifies approximately 95% of APL or CML patients with fusion gene alterations.
The researchers tested the diagnostic on blood and bone marrow samples from patients treated at Dana-Farber, Johns Hopkins Medical Institute, and Brigham and Women’s Hospital, achieving 100% accuracy. Similar results were obtained from dried blood spot samples from CML patients in regions with limited diagnostic resources, including Central America, Africa, Asia, and Oceania.
Future Directions
Funded by the James A. and Lois J. Champy Family Fund, the researchers are collaborating with the Robert and Renee Belfer Center for Applied Cancer Science at Dana-Farber to develop the technology into a commercial product, potentially making it widely accessible to healthcare providers worldwide.
