Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia. Cell Stem Cell 2015 Aug 06;17(2):152-164
Date
07/28/2015Pubmed ID
26212080Pubmed Central ID
PMC4664079DOI
10.1016/j.stem.2015.06.006Scopus ID
2-s2.0-84938741455 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
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.
Author List
Kwon HY, Bajaj J, Ito T, Blevins A, Konuma T, Weeks J, Lytle NK, Koechlein CS, Rizzieri D, Chuah C, Oehler VG, Sasik R, Hardiman G, Reya TAuthor
Nikki K. Lytle PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCarcinogenesis
Cell Movement
Chemokine CXCL12
Genome
Histone-Lysine N-Methyltransferase
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Mice, Inbred C57BL
Mice, Knockout
Myeloid-Lymphoid Leukemia Protein
Neoplastic Stem Cells
Tetraspanins
Xenograft Model Antitumor Assays
