JAK3 Mutations ID'd in About One-Third of T-Cell Lymphomas
(HealthDay News) – Approximately one-third of patients with natural killer/T-cell lymphoma (NKTCL) harbor somatic-activating Janus kinase 3 (JAK3) mutations.
Ghee Chong Koo, PhD, from the National Cancer Centre Singapore, and colleagues conducted whole-exome sequencing in four patients with NKTCLs. In 61 additional cases, the prevalence of JAK3 mutations was investigated using Sanger sequencing and high-resolution melt analysis.
In two of the four patients who underwent whole-exome sequencing, the researchers identified JAK3 somatic-activating mutations (A572V and A573V). Further analysis demonstrated that 35.4% of cases harbored JAK3 mutations. The JAK3 mutations were suggested to be involved in cytokine-independent JAK/STAT constitutive activation, leading to enhanced growth. Inhibition with the novel pan-JAK inhibitor CP-690550 resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis in both JAK3-mutant and wild-type NKTCL cell lines.
"In summary, our studies identified, for the first time, frequent JAK3 mutations in NKTCLs," the authors write. "They also indicated that targeting the JAK/STAT pathway in this disease is a potentially effective therapeutic approach that warrants further investigation."