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

作者: Emmanuelle Passegué , Erwin F Wagner , Irving L Weissman , None

DOI: 10.1016/J.CELL.2004.10.010

关键词: Transcriptional regulationTranscription factorMyelopoiesisHaematopoiesisJUNBStem cellImmunologyCancer researchChronic myelogenous leukemiaProgenitor cellBiology

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

参考文章(48)
Antonio Cozzio, Emmanuelle Passegué, Paul M Ayton, Holger Karsunky, Michael L Cleary, Irving L Weissman, Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors Genes & Development. ,vol. 17, pp. 3029- 3035 ,(2003) , 10.1101/GAD.1143403
Anna V Molofsky, Ricardo Pardal, Toshihide Iwashita, In-Kyung Park, Michael F Clarke, Sean J Morrison, None, Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation Nature. ,vol. 425, pp. 962- 967 ,(2003) , 10.1038/NATURE02060
Ralf Kühn, Frieder Schwenk, Michel Aguet, Klaus Rajewsky, Inducible gene targeting in mice Science. ,vol. 269, pp. 1427- 1429 ,(1995) , 10.1126/SCIENCE.7660125
Daniel G. Tenen, Disruption of differentiation in human cancer: AML shows the way Nature Reviews Cancer. ,vol. 3, pp. 89- 101 ,(2003) , 10.1038/NRC989
Ming-Yu Yang, Ta-Chih Liu, Jan-Gowth Chang, Pai-Mei Lin, Sheng-Fung Lin, JunB gene expression is inactivated by methylation in chronic myeloid leukemia Blood. ,vol. 101, pp. 3205- 3211 ,(2003) , 10.1182/BLOOD-2002-05-1598
Suzanne Maria Vercauteren, Normal and Leukemic Hematopoiesis ,(2003)
G. Bhardwaj, B. Murdoch, D. Wu, D. P. Baker, K. P. Williams, K. Chadwick, L. E. Ling, F. N. Karanu, M. Bhatia, Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation Nature Immunology. ,vol. 2, pp. 172- 180 ,(2001) , 10.1038/84282
Barbara Varnum-Finney, Lanwei Xu, Carolyn Brashem-Stein, Cynthia Nourigat, David Flowers, Sonia Bakkour, Warren S. Pear, Irwin D. Bernstein, Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nature Medicine. ,vol. 6, pp. 1278- 1281 ,(2000) , 10.1038/81390
David Traver, Koichi Akashi, Irving L. Weissman, Eric Lagasse, Mice Defective in Two Apoptosis Pathways in the Myeloid Lineage Develop Acute Myeloblastic Leukemia Immunity. ,vol. 9, pp. 47- 57 ,(1998) , 10.1016/S1074-7613(00)80587-7