JAK inhibition in early-onset somatic, nonclonal STAT5B gain-of-function disease

Abstract

Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways mediate the signaling of multiple cytokines for a myriad of leukocyte functions.1 Somatic gain-of-function (GOF) mutations in STAT5B, especially N642H, are described in multiple neoplasms, in particular leukemia and lymphoma, and can be associated with significant eosinophilia.2-5 A different phenotype for somatic STAT5B N642H mutations has recently been observed whereby a nonmalignant process affects multiple hematopoietic lineages and presents with early-onset, extreme hypereosinophilia with urticaria, dermatitis, and diarrhea.