Dysregulated RPB1 is a targetable master driver of overgrowth in acute myeloid leukemia.

Dysregulated RPB1 is a critical oncogenic hub that drives overgrowth hijacking an array of oncogenic and anti-apoptosis factors.Targeting RPB1 leads to potent regression of human refractory AML in mouse models. Overall design: To reveal the biological basis of POLR2A dependency of AML cells, we performed genetic silence of POLR2A in a highly aggressive human AML cell line MOLM-13 using doxycycline (Dox)-inducible CRISPR/Cas9 mediated POLR2A knockout system, and examined the effects of POLR2A silence on proliferation and viability of MOLM-13 cells. The biological basis of POLR2A between the control and POLR2A-KO cells were generated by deep sequencing, using Illumina HiSeq 4000.