Rapid Blood Cancer Diagnostic Could Speed Decisions and Save Lives

Coleman Lindsley, MD, PhD

Researchers at Dana-Farber Cancer Institute have created a CRISPR-based rapid molecular diagnostic for two forms of leukemia that are driven by mutations that involve gene fusions. The technology accurately detects the presence of these gene fusions in acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) in patient samples.

Precision medicines have long been available for these two forms of leukemia but many care centers are unable to provide timely precision diagnostics for the diseases. This new technology could fill that gap, enabling more patients with these blood cancers to receive lifesaving cancer treatments.

“It doesn't matter if you have highly effective treatment for a disease if you can't diagnose that disease,” says senior author and Dana-Farber physician-scientist Coleman Lindsley, MD, PhD. “By developing rapid, accurate, point-of-care tests for cancer, we hope to improve outcomes by increasing accessibility and timeliness of diagnostic testing.”

The test results can be read out on a lateral flow strip within two hours and were 100% accurate in tests on patient samples. The study is published in Blood.

Today, precision molecular diagnostics are performed on-site at major cancer institutes like Dana-Farber. Most other care centers need to send blood samples out to centralized labs for molecular testing and can take anywhere from a few days to a week to receive results.

In the case of APL, such a delay can be life threatening. Patients who develop APL are at a high risk of death from bleeding during the interval between initial disease onset and the start of treatment. Treatment with all-trans retinoic acid (ATRA), a vitamin A derivative, immediately reverses the bleeding risk. When rapid molecular diagnostics are readily available, fewer than one in ten patients with a fusion gene with die from the disease because they are quickly matched with curative treatments. However, when diagnostics are not readily available, as many as one in three patients dies from the disease while waiting for a diagnosis.

“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,” says first author and Dana-Farber physician-scientist Rahul Vedula, MD.

In the case of CML, there are highly effective and inexpensive oral precision medications available to treat the disease. In countries with limited resources, however, health systems do not have access to diagnostics that enable physicians to diagnose the disease and prescribe the treatments.

“It isn’t known how many people could be receiving treatment, but aren’t, simply because of a lack of accessible diagnostics,” says Vedula.

“We’re trying to fill that accessibility gap,” says Lindsley. “This diagnostic test could be used in a low-resource setting without the need for highly specialized medical training.”

The test searches within a blood sample for strings of RNA, similar to the way a word processor searches for specific words in a document. There are two different known alterations in each disease, so each test is designed to look for those two disease-specific sequences. The tests are highly accurate because the CRISPR mechanism matches only with an exactly matched RNA code. Approximately 95% of patients with APL or CML that have fusion gene alterations have one of these known sequences.

The technology is built on the CRISPR-based SHERLOCK platform, a technology originally invented for infectious disease applications. The team tested the diagnostic on blood and bone marrow samples from patients with APL or CML that had been treated at Dana-Farber, Johns Hopkins Medical Institute, and Brigham and Women’s Hospital. Results were 100% accurate. The team also tested dried blood spot samples from patients with CML from regions with limited diagnostic resources, including Central America, Africa, Asia, and Oceania and found similar results.

Based on the results of this study, which was funded by the James A. and Lois J. Champy Family Fund, the researchers have begun working with the Robert and Renee Belfer Center for Applied Cancer Science at Dana-Farber to develop the technology into a commercial product.