This study also investigated the mechanisms through NPM-ALK induces the OIS in ALCL, showing that p16INK4a is repressed by methylation in its promoter and oncogenic tyrosine kinase induces de-methylation by Jmjd3, a histone lysine demethylase, and then p16INK4a transcription. The gene discussed is NPM1; the disease is anaplastic large cell lymphoma.