Sugar thieves and addicts: Nutrient subversion in JAK2 MPNs

Abstract

Unexplained weight loss and cachexia are key hallmarks of cancer and advanced myeloproliferative neoplasms (MPNs). In this issue of Blood, Rao et al describe their investigation of themetabolic response to JAK2 mutation in mousemodels, which demonstrated that the presence of the JAK2-mutant clone leads to hypoglycemia and adipose tissue atrophy as a result of scavenging nutrients to meet the increased glucose requirements of erythroid precursors.1 They identify the enzyme Pfkfb3 as a key mediator of glycolysis and show that inhibition of Pfkfb3 reverses hypoglycemia and reduces the hematopoietic manifestations of the disease. These data offer a first mechanistic insight into a poorly characterized aspect ofMPN disease biology, and provide a clear preclinical rationale for further investigation of the metabolome as a therapeutic target.