RNA-seq analysis of THP-1 cell line upon knockdown of CHD4. RNA-seq analysis of THP-1 cell line upon knockdown of CHD4

Epigenetic alterations contribute to leukemogenesis in childhood acute myeloid leukemia (AML). We used RNAi screens of AML cells together with non-transformed bone marrow cells and identified CHD4 as being required for AML maintenance. RNAi and CRISPR-Cas9 approaches, showed that CHD4 is essential for cell growth of leukemic cells in vitro, and disease progression in vivo, including primary childhood AML cells. Loss of function of CHD4 arrests AML cells in the G0 phase of the cell cycle, which is associated with downregulation of MYC and its target genes. Conversely, CHD4 suppression is not essential for normal blood cells. Taken together, our results identify CHD4 as a potential therapeutic target in childhood AML. Overall design: THP-1 cell line were trasnduced with shRNA targeting CHD4 or negative control vectors and RNA was isolated for RNA-seq analysis 72hour post transduction.