Molecular Testing for Myeloproliferative Neoplasms
Testing myeloproliferative neoplasms (MPNs) produces more than its fair share of negative results. However, a negative result can have a variety of meanings. While some results may not be good news, they might not be any news at all. CAP Today interviewed several experts in the field about molecular testing for MPNs and the significance of the results.
The article discusses the discovery, in late 2013, of two new, highly relevant diagnostic mutations, CSF3R and CALR (calreticulin), and their effect in MPN molecular testing. According to Ayalew Tefferi, M.D., professor of medicine and hematology at Mayo Clinic, Rochester, Minn, new mutations are significant. However, despite its importance, molecular testing—or even next-generation sequencing—isn't particularly special.
“The tools are different, but there are always new tools,” says Dr. Tefferi. “It’s like children: When there are new toys, they want new toys. But the concept is the same; the concepts don’t change.”
Dr. Tefferi goes on to discuss morphology's strengths. “Morphology can tell us so much,” he says. “The problem is, other scientists and clinicians who are not trained as pathologists can’t appreciate that. They think it’s too subjective.”
In addition to the discussion of molecular testing, the article assess the value of next-generation sequencing (NGS) for MPNs. Dr. Tefferi understands the allure. At Mayo, he has access to seemingly limitless MPN genetic data, and he’s doing his best to put it to good use. “We’ve stored a lot of patient samples over the years,” he says, “and there’s complete follow-up of many of these patients.” His goal is to provide rock-solid data to support the value of a mutation in diagnosis or prognosis. Only then, he says, will organizations such as WHO advocate a test’s use. Only then will payers pony up. And only then will it make sense for a laboratory to add the test to its menu.
While next-generation sequencing might seem like the logical step, Dr. Tefferi is cautious. “The problem with that is, you have to show me that approach actually helps patients,” Dr. Tefferi says. Looking at the newer mutations, he says, it’s clear that CALR is important; so is ASXL1, which is prognostically valuable not only in MPNs but also in myelodysplastic syndromes and other disorders. “But does the patient need 33 mutations? Why?”
While Dr. Tefferi makes an interesting advocate for traditional methodologies, he is not rejecting NGS outright. In his own research, NGS helps him sort through cases where multiple mutations may be in play. He’s currently using NGS to explore the quantitative value—allele burden as well as the number of mutations—in PV, ET, and myelofibrosis.
According to Dr. Tefferi, “If a molecular result is negative, it doesn’t mean the mutation isn’t there. How do we know if something exists? If a tree falls in the forest and no one is there to hear it, does it still make a sound? It just means I need to look at this a little more in depth. Be a good clinician. If we can get that into our heads, we’ll be OK.”
Read the full article to learn more industry perspectives on molecular testing for MPNs.