Myeloproliferative Neoplasms: Managing the Cup that Runneth Over
In his seminal review, Dr. William Dameshek speculated on a shared pathogenesis, and the likelihood of a "myelostimulatory factor" in the entities now known as Myeloproliferative Neoplasms. The discovery of JAK2 V617F ushered in a new era of understanding, and nearly 15 years later, the molecular landscape of the MPNs has been increasingly characterized. It is now understood that some patients are genetically predisposed to MPNs, or have hereditary, but non-clonal cytosis. However, establishing these diagnoses can be challenging. While the thrombotic tendency in the MPNs has been long recognized, defining key pathophysiological contributions remains an important goal. Recent work implicates JAK2 V617F as a prominent driver of the thrombotic tendency. Finally, while the JAK2 V617F discovery heralded development of JAK-inhibitors, a more complete understanding of the MPN pathogenesis has paved the way for development of novel therapies. The current landscape of MPN clinical trials is unprecedented, and hopefully, agents which clearly impact natural history will emerge.
Dr. Mary Frances McMullin will review the causes of hereditary erythrocytosis and thrombocytosis and distinguish from the genetic factors contributing to familial myeloproliferative disorders. The diagnostic pathways leading to diagnosis of hereditary disorders will be discussed.
Dr. Brady Stein will discuss the traditional and novel risk factors for MPN-thrombosis, in addition to contemporary risk classification. Treatment strategies to reduce risk for incident and recurrent thrombosis will be reviewed. Finally, an approach to management of special situations, including unusual site thrombosis, and MPN-bleeding will be discussed.
Within the context of current treatments that center on the JAK-STAT pathway, Dr. Aaron Gerds will review how emerging treatments are now reaching for new targets beyond JAK-STAT based on an ever-increasing understanding of the complex pathobiology of Ph-negative MPNs.
Mary Frances McMullin
Active, International, Emeritus, and Honorary Members
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