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JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells.

The AP-1 transcription factor JunB is a transcriptional regulator of myelopoiesis. Inactivation of JunB in postnatal mice results in a myeloproliferative disorder (MPD) resembling early human chronic myelogenous leukemia (CML). Here, we show that JunB regulates the numbers of hematopoietic stem cells (HSC). JunB overexpression decreases the frequency of long-term HSC (LT-HSC), while JunB inactivation specifically expands the numbers of LT-HSC and granulocyte/macrophage progenitors (GMP) resulting in chronic MPD. Further, we demonstrate that junB inactivation must take place in LT-HSC, and not at later stages of myelopoiesis, to induce MPD and that only junB-deficient LT-HSC are capable of transplanting the MPD to recipient mice. These results demonstrate a stem cell-specific role for JunB in normal and leukemic hematopoiesis and provide experimental evidence that leukemic stem cells (LSC) can reside at the LT-HSC stage of development in a mouse model of MPD.

Pubmed ID: 15507213

Authors

  • Passegu√© E
  • Wagner EF
  • Weissman IL

Journal

Cell

Publication Data

October 29, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: CA55209
  • Agency: NCI NIH HHS, Id: CA86017

Mesh Terms

  • Animals
  • Apoptosis
  • Cell Division
  • Cell Transformation, Neoplastic
  • Hematopoietic Stem Cells
  • Mice
  • Myeloproliferative Disorders
  • Proto-Oncogene Proteins c-jun