The Wilms tumor suppressor WT1 directs stage-specific quiescence and differentiation of human hematopoietic progenitor cells

EMBO J. 2001 Apr 17;20(8):1897-909. doi: 10.1093/emboj/20.8.1897.


WT1, a transcription factor implicated in both normal kidney differentiation and tumorigenesis, is also expressed in differentiating hematopoietic progenitors. Most human acute leukemias contain high levels of the wild-type transcript, while a minority have point mutations, raising the possibility that this tumor suppressor might have a paradoxical oncogenic effect in some hematopoietic cells. Using high titer retroviral infection, we demonstrate that WT1 triggers rapid growth arrest and lineage-specific differentiation in primary hematopoietic progenitors and differentiation-competent leukemia cell lines, while it induces cellular quiescence in a primitive subset of primary precursors. Growth arrest by WT1 is associated with induction of p21(CIP1), but expression of this cyclin-dependent kinase inhibitor alone is insufficient for either cellular differentiation or primitive cell preservation. The effects of WT1 are enhanced by co-expression of its naturally occurring isoforms, and are correlated with the physiological expression pattern of WT1 in vivo. Our observations suggest a role for WT1 in the differentiation of human hematopoietic cells, and provide a functional model that supports its capacity as a tumor suppressor in human acute leukemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Genes, Tumor Suppressor*
  • Genetic Vectors
  • Hematopoiesis / genetics
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Leukemia / etiology
  • Monocytes / cytology
  • Retroviridae / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • WT1 Proteins
  • Wilms Tumor*


  • DNA-Binding Proteins
  • Transcription Factors
  • WT1 Proteins