| First Author | Passegué E | Year | 2004 |
| Journal | Cell | Volume | 119 |
| Issue | 3 | Pages | 431-43 |
| PubMed ID | 15507213 | Mgi Jnum | J:94778 |
| Mgi Id | MGI:3521518 | Doi | 10.1016/j.cell.2004.10.010 |
| Citation | Passegue E, et al. (2004) JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells. Cell 119(3):431-43 |
| abstractText | 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. |
