A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence

Bin Lu, Olaf Klingbeil, Yusuke Tarumoto, Tim D.D. Somerville, Yu Han Huang, Yiliang Wei, Dorothy C. Wai, Jason K.K. Low, Joseph P. Milazzo, Xiaoli S. Wu, Zhendong Cao, Xiaomei Yan, Osama E. Demerdash, Gang Huang, Joel P. Mackay, Justin B. Kinney, Junwei Shi, Christopher R. Vakoc

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The Mixed Lineage Leukemia gene (MLL) is altered in leukemia by chromosomal translocations to produce oncoproteins composed of the MLL N-terminus fused to the C-terminus of a partner protein. Here, we used domain-focused CRISPR screening to identify ZFP64 as an essential transcription factor in MLL-rearranged leukemia. We show that the critical function of ZFP64 in leukemia is to maintain MLL expression via binding to the MLL promoter, which is the most enriched location of ZFP64 occupancy in the human genome. The specificity of ZFP64 for MLL is accounted for by an exceptional density of ZFP64 motifs embedded within the MLL promoter. These findings demonstrate how a sequence anomaly of an oncogene promoter can impose a transcriptional addiction in cancer.

Original languageEnglish (US)
Pages (from-to)970-981.e8
JournalCancer Cell
Issue number6
StatePublished - Dec 10 2018
Externally publishedYes


  • addiction
  • CRISPR screen
  • leukemia
  • MLL
  • motif
  • oncogene
  • promoter
  • ZFP64

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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