The transcription factor STAT6 regulates expression of genes that promote survival, proliferation, and self-renewal in B lymphocytes. STAT6 is constitutively activated in the majority of cases of PMBL through activation of tyrosine kinases or inactivation of negative regulators such as phosphatases, proteases, and suppressors of cytokine signaling. However, the role of recently discovered point mutations in the DNA binding domain of STAT6 in PMBL remains to be determined.