Jon Aster, MD, PhD
The Rapid Heme Panel really was developed based on our discussions with our clinical colleagues at the Dana Farber Cancer Institute and here at Brigham and Women's Hospital. The clinicians are involved with treating blood cancers. We all came to a consensus that we needed a rapid turnaround test that would be highly focused on the genes that are most important in driving the pathogenesis of blood cancers.
A group of us came together: myself, Rich Stone and Dan DeAngelo, who lead the Leukemia Program at Dana Farber Cancer Institute, together with Frank Kuo and Mike Kluk, who are in the Center for Advanced Molecular Diagnostics here at Brigham and Women's Hospital, to create a new DNA-based test which relies on relatively new technology that allows us to do a very deep screen across 95 genes which are among the most commonly mutated genes in acute leukemias, myelodysplastic syndromes and myeloproliferative neoplasms; and this allows us to make rapid refined diagnoses where we can tell the clinicians what the molecular events are that are making the diseases that they're treating in their patients, what's making them tick.
Right now we're using it in acute leukemias, which can be either acute lymphoid leukemia, acute myeloid leukemia. And we're also using it broadly in what are called the myeloid neoplasms, which include not only AML, acute myeloid leukemia, but also myelodysplastic syndromes and myeloproliferative neoplasms, in part because those diseases, myelodysplastic syndrome or MDS and myeloproliferative neoplasms are often, frankly, quite difficult to diagnose with the usual tools. Patients will come in and they'll have abnormal blood counts. The cause is often unclear. And this test can be very helpful in identifying the molecular lesions that tell us that indeed this is a patient with a myeloid neoplasm or on the other hand is a patient who probably doesn't have a neoplasm, where the clinicians have to go and look for another cause for their abnormal blood counts.
The test based on our experience so far is probably done as easily on peripheral blood as it is on bone marrow. So, in most cases we simply draw a tube of blood from the patient. The blood is then sent to the Center for Advanced Molecular Diagnosis, where we process the blood cells into DNA and then over a period of about a day there are a series of reactions that take place that prepare the DNA for sequencing, that then goes on a special sequencing instrument called a MiSeq instrument, which overnight will generate the sequence reads. And then we have to look at the data, sit down and identify the sequence variants and also make a decision about whether the sequence variants that we see, whether they're meaningful, whether they're actually pathogenic and likely to be causing the disease in the patient.
By way of comparison, before this test was available, we were doing single gene testing as send-outs to outside laboratories that offered tests for individual genes that are in the panel and the turnaround time for those individual genes would be as much as two to three weeks. And moreover, the expense for a single gene test as a send-out was greater than the expense for the 95-gene panel done in-house. So, we can provide much deeper information across a much larger number of genes in less time, at a fraction of the original cost.
I think the most dramatic change in outcome is we're hopeful that it will enable patients with, for example, acute leukemia, who failed other kinds of therapies to very quickly be placed on appropriate clinical trials with targeted agents. So, for example, IDH1 and IDH2 are two genes that are tested in the Rapid Heme Panel for which there are new drugs that are available, and there is emerging data that these agents, these agents that target these two mutated genes, they only work in acute myeloid leukemias that have mutations in IDH1 or IDH2, that for some patients these are going to be absolutely lifesaving.
I think the Rapid Heme Panel is an exceptional example of the kind of innovation that we see consistently across the Dana-Farber/Brigham and Women's Cancer Center. Obviously, one key thing is to have a diverse group of people with the skill sets that can produce this kind of a test. You need pathologists, you need informed oncologists, you need people in basic science laboratories who are interested in clinical translation who can also work together well as a team.
In addition to just getting the diagnosis right, another added value which I think we're going to be expanding upon as we add tests in the Center for Advanced Molecular Diagnosis, is our ability to increasingly identify the specific molecular lesions that are driving that particular patient's cancer, which increasingly as we go forward is going to enable precision cancer medicine and precision cancer therapeutics.
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