Dr. Mascarenhas on the Role of Genetic Testing in MPNs

John O. Mascarenhas, MD, associate professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai, director of the Adult Leukemia Program, and leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai, and a member of the Tisch Cancer Institute, discusses the role of genetic testing in myeloproliferative neoplasms (MPNs).

At most cancer centers, genetic testing is typically performed at the time of diagnosis or if a patient’s diagnosis changes, explains Mascarenhas. At initial diagnosis, next-generation sequencing (NGS) may be performed if the patient’s bone marrow biopsy shows that their blood is not able to be aspirated. Physician preference often determines which NGS panel is utilized, Mascarenhas says.

Typically, NGS panels test for myeloid-associated genetic mutations commonly found in patients with myelodysplastic syndrome, MPNs, or acute myeloid leukemia, says Mascarenhas. Moreover, identification of driver mutations, such as JAK2, CALR, and MPL, can confer prognostic significance. Additionally, the absence of these driver mutations indicates triple-negative disease, which is also prognostic.

Currently, genetic testing results do not have therapeutic implications, Mascarenhas explains. However, immunotherapeutic agents directed toward calreticulin are in development as the gene codes for a potentially targetable cell surface mutation. Ultimately, MPNs are complex diseases so prognostically significant subclonal mutations are used in risk stratification, concludes Mascarenhas.