Closing the gap: Genetic landscape of MPN

Abstract

In this issue of Blood, Milosevic Feenstra et al1 and Cabagnols et al2 report the discovery of heterogeneous novel mutations in MPL and JAK2 genes in 5% to 10% of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients who lacked what are regarded as classical mutations in these myeloproliferative neoplasms (MPNs) and were thereby considered as having a "triple-negative" (TN) disease. The concept of TN ET and PMF patients was developed after the discovery of calreticulin (CALR) mutations.3,4 The term "triple negativity" was first employed for breast cancer patients who had tumors negative for estrogen or progesterone receptor and HER2 mutations, but it is no longer scientifically correct. TN breast cancers have subsequently been shown to harbor pathogenic mutations in several other genes, including PI3KCA, BRCA1, BRCA2, and PALB2,which are now of increasing importance in clinical management.5 The findings in these 2 manuscripts for TN ET and PMF patients are similarly important and raise several questions for both future research and clinical practice.