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
- Passegué E
- Wagner EF
- Weissman IL
October 29, 2004
- Agency: NCI NIH HHS, Id: CA55209
- Agency: NCI NIH HHS, Id: CA86017
- Cell Division
- Cell Transformation, Neoplastic
- Hematopoietic Stem Cells
- Myeloproliferative Disorders
- Proto-Oncogene Proteins c-jun