Please use this identifier to cite or link to this item: https://doi.org/10.1172/JCI62891
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dc.titleA SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis
dc.contributor.authorLi, A.
dc.contributor.authorYang, Y.
dc.contributor.authorGao, C.
dc.contributor.authorLu, J.
dc.contributor.authorJeong, H.-W.
dc.contributor.authorLiu, B.H.
dc.contributor.authorTang, P.
dc.contributor.authorYao, X.
dc.contributor.authorNeuberg, D.
dc.contributor.authorHuang, G.
dc.contributor.authorTenen, D.G.
dc.contributor.authorChai, L.
dc.date.accessioned2014-12-12T07:46:59Z
dc.date.available2014-12-12T07:46:59Z
dc.date.issued2013-10-01
dc.identifier.citationLi, A., Yang, Y., Gao, C., Lu, J., Jeong, H.-W., Liu, B.H., Tang, P., Yao, X., Neuberg, D., Huang, G., Tenen, D.G., Chai, L. (2013-10-01). A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis. Journal of Clinical Investigation 123 (10) : 4195-4207. ScholarBank@NUS Repository. https://doi.org/10.1172/JCI62891
dc.identifier.issn00219738
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/116204
dc.description.abstractThe embryonic self-renewal factor SALL4 has been implicated in the development of human acute myeloid leukemia (AML). Transgenic mice expressing the human SALL4B allele develop AML, which indicates that this molecule contributes to leukemia development and maintenance. However, the underlying mechanism of SALL4-dependent AML progression is unknown. Using SALL4B transgenic mice, we observed that HoxA9 was significantly upregulated in SALL4B leukemic cells compared with wild-type controls. Downregulation of HoxA9 in SALL4B leukemic cells led to decreased replating capacity in vitro and delayed AML development in recipient mice. In primary human AML cells, downregulation of SALL4 led to decreased HOXA9 expression and enhanced apoptosis. We found that SALL4 bound a specific region of the HOXA9 promoter in leukemic cells. SALL4 overexpression led to enhanced binding of histone activation markers at the HOXA9 promoter region, as well as increased HOXA9 expression in these cells. Furthermore, we observed that SALL4 interacted with mixed-lineage leukemia (MLL) and co-occupied the HOXA9 promoter region with MLL in AML leukemic cells, which suggests that a SALL4/MLL pathway may control HOXA9 expression. In summary, our findings revealed a molecular mechanism for SALL4 function in leukemogenesis and suggest that targeting of the SALL4/MLL/HOXA9 pathway would be an innovative approach in treating AML.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1172/JCI62891
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.1172/JCI62891
dc.description.sourcetitleJournal of Clinical Investigation
dc.description.volume123
dc.description.issue10
dc.description.page4195-4207
dc.description.codenJCINA
dc.identifier.isiut000325443100016
Appears in Collections:Staff Publications

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