JAK3 Mutations ID'd in About One-Third of T-Cell Lymphomas

Somatic activating mutation in JAK3 (A572V and A573V) identified in natural killer/T-cell lymphoma

FRIDAY, June 15 (HealthDay News) -- Approximately one-third of patients with natural killer/T-cell lymphoma (NKTCL) harbor somatic-activating Janus kinase 3 (JAK3) mutations, according to a study published online June 15 in Cancer Discovery.

Ghee Chong Koo, Ph.D., 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 percent 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."

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