Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia

Hyog Young Kwon, Jeevisha Bajaj, Takahiro Ito, Allen Blevins, Takaaki Konuma, Joi Weeks, Nikki K. Lytle, Claire S. Koechlein, David Rizzieri, Charles Chuah, Vivian G. Oehler, Roman Sasik, Gary Hardiman, Tannishtha Reya*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Summary Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults and children and is frequently resistant to therapy. Thus, identifying signals needed for AML propagation is a critical step toward developing new approaches for treating this disease. Here, we show that Tetraspanin 3 is a target of the RNA binding protein Musashi 2, which plays a key role in AML. We generated Tspan3 knockout mice that were born without overt defects. However, Tspan3 deletion impaired leukemia stem cell self-renewal and disease propagation and markedly improved survival in mouse models of AML. Additionally, Tspan3 inhibition blocked growth of AML patient samples, suggesting that Tspan3 is also important in human disease. As part of the mechanism, we show that Tspan3 deficiency disabled responses to CXCL12/SDF-1 and led to defects in AML localization within the niche. These identify Tspan3 as an important regulator of aggressive leukemias and highlight a role for Tspan3 in oncogenesis.

Original languageEnglish
Article number1796
Pages (from-to)152-164
Number of pages13
JournalCell Stem Cell
Volume17
Issue number2
DOIs
Publication statusPublished - 06 Aug 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Kwon, H. Y., Bajaj, J., Ito, T., Blevins, A., Konuma, T., Weeks, J., Lytle, N. K., Koechlein, C. S., Rizzieri, D., Chuah, C., Oehler, V. G., Sasik, R., Hardiman, G., & Reya, T. (2015). Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia. Cell Stem Cell, 17(2), 152-164. [1796]. https://doi.org/10.1016/j.stem.2015.06.006