Abstract
Janus Kinase 3 (JAK3) is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic cells, that plays an essential role in hematopoiesis during T cell development. JAK3 somatic-activating mutations were identified in extranodal natural killer/T cell lymphomas (ENKTL) in recent cases in Singapore. We hypothesized these mutations might play an important role in the pathogenesis of T and NK cell neoplasms in other areas of the world. We performed JAK3 exon13 sequencing for different types of T and NK cell neoplasms including ENKTL (59 cases total). We identified four mutations in three (5.0%) cases. All of the mutations were from ENKTL cases (15.8%). Among the four newly found mutations, three are silent mutations and one introduces a stop codon, which was not an activating mutation as in the cases in Singapore. We detected four (30.8%) cases positive for phosphorylated JAK3 expression among 13 NKTCL cases when we performed JAK3 (phospho Y785) immunostaining on sections of ENKTL samples. It seems that phosphorylated JAK3 expression does not necessarily harbor exon 13 mutations. The mechanism responsible for activating expression of the gene will be a topic for further research.