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Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia

Wei, Junping, Wunderlich, Mark, Fox, Catherine, Alvarez, Sara, Cigudosa, Juan C., Wilhelm, Jamie S., Zheng, Yi, Cancelas, Jose A., Gu, Yi, Jansen, Michael, DiMartino, Jorge F., Mulloy, James C.·2008·Cancer Cell
DOI 10.1016/j.ccr.2008.04.020
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Abstract

Faithful modeling of mixed-lineage leukemia in murine cells has been difficult to achieve. We show that expression of MLL-AF9 in human CD34+ cells induces acute myeloid, lymphoid, or mixed-lineage leukemia in immunodeficient mice. Some leukemia stem cells (LSC) were multipotent and could be lineage directed by altering either the growth factors or the recipient strain of mouse, highlighting the importance of microenvironmental cues. Other LSC were strictly lineage committed, demonstrating the heterogeneity of the stem cell compartment in MLL disease. Targeting the Rac signaling pathway by pharmacologic or genetic means resulted in rapid and specific apoptosis of MLL-AF9 cells, suggesting that the Rac signaling pathway may be a valid therapeutic target in MLL-rearranged AML.

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Research works printed but not linked: 37

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Cited by

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Metadata

Authors
Wei, J., Wunderlich, M., Fox, C., Alvarez, S., Cigudosa, J. C., Wilhelm, J. S., Zheng, Y., Cancelas, J. A., Gu, Y., Jansen, M., DiMartino, J. F., & Mulloy, J. C.
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2008-06
Volume
13
Issue
6
Pages
483-495
ISSN
1535-6108
DOI
10.1016/j.ccr.2008.04.020
Cited by
284
References
7
Language
en
Licence

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CoChat. (2026). Citation check: Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia. https://app.cochat.ai/papers/10.1016/j.ccr.2008.04.020
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Wei, J., Wunderlich, M., Fox, C., Alvarez, S., Cigudosa, J. C., Wilhelm, J. S., Zheng, Y., Cancelas, J. A., Gu, Y., Jansen, M., DiMartino, J. F., & Mulloy, J. C. (2008). Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia. Cancer Cell. https://doi.org/10.1016/j.ccr.2008.04.020