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As compared to normal tonsil B cells, MCL cells showed higher activation of the JNK MAPK in both an MAPK array and a sandwich ELISA assay. Immunohistochemistry showed overexpression of phospho (p)\u2010JNK (Thr183\/Tyr185) in 30 of 37 MCL cases. Inhibition of p\u2010JNK with SP600125 resulted in growth arrest in all four MCL cell lines (Jeko\u20101, HBL\u20102, UPN\u20101, Granta\u2010519), which could be partly reversed by the addition of CD40L and IL\u20104. Furthermore, SP600125 led to G2\/M phase arrest on day 1 and a striking increase in endoreduplication on day 2 and day 3, which was confirmed by karyotype analysis. G2\/M arrest was associated with down\u2010regulation of EGR1 and p21 protein expression. SP600125\u2010induced polyploidy could be blocked by the BCL\u20102 inhibitor YC137. These data suggest that constitutive JNK activity is necessary to promote proliferation and maintain diploidy in MCL. JNK inhibition leads to cell cycle deregulation and endoreduplication, mimicking the tetraploid state seen in a subset of MCL cases. Thus, our data also provide an experimental model to study polyploid MCL cells. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2521","type":"journal-article","created":{"date-parts":[[2009,1,13]],"date-time":"2009-01-13T09:40:20Z","timestamp":1231839620000},"page":"95-103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["JNK is constitutively active in mantle cell lymphoma: cell cycle deregulation and polyploidy by JNK inhibitor 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