Researchers have developed a rapid molecular diagnostic tool using CRISPR technology to detect two types of leukemia caused by gene fusion mutations. This method effectively identifies these gene fusions in both acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) in patient samples.
A team at Dana-Farber Cancer Institute has crafted a swift, CRISPR-based molecular diagnostic aimed at two leukemia types influenced by gene fusion mutations. This innovative tool can accurately find these gene fusions in patient samples of acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML).
Although there are already precision medicines available for these leukemia types, many medical facilities struggle to provide timely diagnostic services. This new technology could bridge that gap, allowing more patients suffering from these types of blood cancer to access critical treatments.
“Having effective treatments means little if we can’t successfully diagnose the disease,” explains Coleman Lindsley, MD, PhD, a senior author and physician-scientist at Dana-Farber. “By creating quick, reliable tests that can be performed on-site, we aim to enhance patient outcomes by making diagnostic testing more accessible and timely.”
The test results can be displayed on a lateral flow strip in under two hours, and tests on patient samples showed 100% accuracy. The findings are featured in the journal Blood.
Currently, precision molecular diagnostics are only carried out at significant cancer centers such as Dana-Farber. Most other healthcare facilities must send blood samples to centralized laboratories for testing, which can result in waits of several days to a week for results.
For APL, such delays can pose serious risks. Patients diagnosed with APL are particularly vulnerable to fatal bleeding during the waiting period between initial symptoms and the commencement of treatment. Administering all-trans retinoic acid (ATRA), a vitamin A derivative, can promptly reduce bleeding risks. When rapid molecular diagnostics are available, less than 10% of patients with a fusion gene die as they quickly receive effective treatments. Conversely, when diagnostic tools are not accessible, nearly one in three patients may succumb to the disease while waiting for a diagnosis.
“Our test can directly be used at the point of care, allowing an emergency room doctor to determine within a few hours if the patient needs this crucial life-saving medication,” states first author and Dana-Farber physician-scientist Rahul Vedula, MD.
For CML, effective and affordable oral precision medications are available. However, in resource-limited countries, health systems often lack the diagnostic tools needed for proper diagnosis and treatment prescriptions.
“We’re unaware of how many individuals may be missing out on treatment simply due to the absence of accessible diagnostics,” remarks Vedula.
“Our goal is to address this accessibility issue,” adds Lindsley. “This diagnostic tool could function in low-resource environments without requiring extensive medical training.”
The test works by searching for specific RNA sequences in a blood sample, akin to how a word processor looks for specified words in a text. Each leukemia has two known alterations, so the test is particularly designed to seek out these disease-specific sequences. The high accuracy of the tests is a result of the CRISPR mechanism, which matches only perfectly aligned RNA codes. Nearly 95% of APL or CML patients with fusion gene changes contain these known sequences. The technology utilizes the CRISPR-based SHERLOCK platform, which was initially developed for infectious disease diagnostics. Researchers tested this diagnostic on blood and bone marrow samples from APL or CML patients treated at Dana-Farber, Johns Hopkins Medical Institute, and Brigham and Women’s Hospital, achieving perfect accuracy. They also evaluated dried blood spot samples from CML patients in areas with limited diagnostic capabilities across Central America, Africa, Asia, and Oceania, yielding similar results.
This study, funded by the James A. and Lois J. Champy Family Fund, has led the researchers to collaborate with the Robert and Renee Belfer Center for Applied Cancer Science at Dana-Farber to turn this technology into a commercially viable product.
