STAT5B N642H drives transformation of NKT cells: a novel mouse model for CD56 + T-LGL leukemia

摘要

The signal transducer and activator of transcription 5B(STAT5B), downstream of IL-15 signaling and Janus kinase(JAK)1, and 3-mediated activation, is a master regulatorof development, survival, and function of innate and innatelike lymphocytes (including natural killer (NK) and NKTcells) [1–3]. Gain-of-function mutations in the SH2 domain ofhuman STAT5B, especially STAT5BN642H, are associatedwith aggressive forms of CD56+ T cell (NKT) and NK celllymphomas/leukemias [4–6]. We described a mouse modelexpressing human (h)STAT5BN642H under the Vav-1 promoter, which develops severe CD8+ T cell neoplasia [7].Here, we explore the ability of hSTAT5BN642H to serve asan oncogenic driver in innate lymphocyte neoplasms.