Cooperative Epigenetic Remodeling By Tet2 Loss And Nras Mutation Drives Myeloid Transformation And Mek Inhibitor Sensitivity
Cancer Cell(2016)
摘要
Epigenetic modifiers and signaling factors are frequently mutated and often co-occur in various myeloid malignancies. However, precisely how these mutations cooperate to cause myeloid leukemia is not fully understood. Here, we show that cells with concurrent Ten-eleven-translocation 2 (Tet2) loss and Nras mutation can cause lethal chronic myelomonocytic leukemia (CMML) like disease in vivo and synergistically activate Ras signaling through epigenetic silencing of Sprouty 2 (Spry2), thereby making cells with both disease alleles dependent on MAPK signaling and highly sensitive to MEK inhibition.
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关键词
leukemia biology,cancer epigenetics,targeted therapeutics
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