LEE011 and ruxolitinib: a synergistic drug combination for natural killer/T-cell lymphoma (NKTCL)

Oncotarget
Yan Ting HeeWee-Joo Chng

Abstract

Natural killer/T-cell lymphoma (NKTCL) is an aggressive non-Hodgkin lymphoma that has been facing limited success with conventional treatments, urging for the discovery of alternative strategies. Recent studies including ours have revealed that EZH2 and JAK-STAT signalling pathways are key contributors to NKTCL pathogenesis. In particular, we found that EZH2 is overexpressed and directly transcriptionally activates the CCND1 gene to confer growth advantage. CCND1 codes for cyclin D1, which complexes with CDK4/6 to promote G1 to S phase transition. Therefore in this study we investigated whether inhibiting both JAK1/2 and CDK4/6, using LEE011 and ruxolitinib respectively is effective in NKTL. We first demonstrate that separate LEE011 and ruxolitinib treatment is sufficient to cause growth inhibition of NKTCL cells. More importantly, we found that there is synergistic growth inhibitory effects on NKTCL cells with combination treatment of LEE011 and ruxolitinib. The results obtained shows that the targeting of both CDK4/6 and JAK1/2 are promising to develop better treatment alternatives for NKTCL.

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Citations

Jun 13, 2019·Hematological Oncology·Jie Xiong, Weili Zhao
Dec 6, 2018·Journal of Hematology & Oncology·Jie Xiong, Wei-Li Zhao
Apr 3, 2019·Journal of Hematology & Oncology·Sanjay de MelSiok-Bian Ng

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

GraphPad Prism
CompuSyn
GraphPad

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