ZFX controls propagation and prevents differentiation of acute T-lymphoblastic and myeloid leukemia

Cell Rep. 2014 Feb 13;6(3):528-40. doi: 10.1016/j.celrep.2014.01.007. Epub 2014 Jan 30.


Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / pathology
  • Clone Cells
  • Gene Expression Regulation, Leukemic
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology*
  • Mice
  • Mitochondria / enzymology
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phenotype
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptors, Notch / metabolism


  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • Receptors, Notch
  • zinc finger protein, X-linked
  • Isocitrate Dehydrogenase
  • Ptpmt1 protein, mouse
  • PTEN Phosphohydrolase