Please use this identifier to cite or link to this item:
|Title:||Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells|
|Source:||Zhang, Y., Yan, X., Sashida, G., Zhao, X., Rao, Y., Goyama, S., Whitman, S.P., Zorko, N., Bernot, K., Conway, R.M., Witte, D., Wang, Q.-F., Tenen, D.G., Xiao, Z., Marcucci, G., Mulloy, J.C., Grimes, H.L., Caligiuri, M.A., Huang, G. (2012-08-02). Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood 120 (5) : 1118-1129. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2012-02-412379|
|Abstract:||One mechanism for disrupting the MLL gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is through partial tandem duplication (MLL-PTD); however, the mechanism by which MLL-PTD contributes to MDS and AML development and maintenance is currently unknown. Herein, we investigated hematopoietic stem/progenitor cell (HSPC) phenotypes of Mll-PTD knock-in mice. Although HSPCs (Lin -Sca1 +Kit + (LSK)/SLAM + and LSK) in Mll PTD/WT mice are reduced in absolute number in steady state because of increased apoptosis, they have a proliferative advantage in colony replating assays, CFU-spleen assays, and competitive transplantation assays over wild-type HSPCs. The Mll PTD/WT-derived phenotypic short-term (ST)-HSCs/multipotent progenitors and granulocyte/ macrophage progenitors have self-renewal capability, rescuing hematopoiesis by giving rise to long-term repopulating cells in recipient mice with an unexpected myeloid differentiation blockade and lymphoid-lineage bias. However, Mll PTD/WT HSPCs never develop leukemia in primary or recipient mice, suggesting that additional genetic and/or epigenetic defects are necessary for full leukemogenic transformation. Thus, the Mll-PTD aberrantly alters HSPCs, enhances self-renewal, causes lineage bias, and blocks myeloid differentiation. These findings provide a framework by which we can ascertain the underlying pathogenic role of MLL-PTD in the clonal evolution of human leukemia, which should facilitate improved therapies and patient outcomes. © 2012 by The American Society of Hematology.|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 28, 2018
WEB OF SCIENCETM
checked on Feb 20, 2018
checked on Mar 12, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.