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. 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.