Alba Maiques-Diaz, Gary J Spencer, James T Lynch, Filippo Ciceri, Emma L Williams, Fabio M R Amaral, Daniel H Wiseman, William J Harris, Yaoyong Li, Sudhakar Sahoo, James R Hitchin, Daniel P Mould, Emma E Fairweather, Bohdan Waszkowycz, Allan M Jordan, Duncan L Smith, Tim C P Somervaille
Pharmacologic inhibition of LSD1 promotes blast cell differentiation in acute myeloid leukemia (AML) with MLL translocations. The assumption has been that differentiation is induced through blockade of LSD1's histone demethylase activity. However, we observed that rapid, extensive, drug-induced changes in transcription occurred without genome-wide accumulation of the histone modifications targeted for demethylation by LSD1 at sites of LSD1 binding and that a demethylase-defective mutant rescued LSD1 knockdown AML cells as efficiently as wild-type protein...
March 27, 2018: Cell Reports