CD34 + /CD38 − acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells
2012; Wiley; Volume: 132; Issue: 9 Linguagem: Inglês
10.1002/ijc.27904
ISSN1097-0215
AutoresChie Nishioka, Takayuki Ikezoe, Mutsuo Furihata, Jing Yang, Satoshi Serada, Tetsuji Naka, Atsuya Nobumoto, Sayo Kataoka, Masayuki Tsuda, Keiko Udaka, Akihito Yokoyama,
Tópico(s)Hematopoietic Stem Cell Transplantation
ResumoAbstract To identify molecular targets in leukemia stem cells (LSCs), this study compared the protein expression profile of freshly isolated CD34 + /CD38 − cells with that of CD34 + /CD38 + counterparts from individuals with acute myelogenous leukemia ( n = 2, AML) using isobaric tags for relative and absolute quantitation (iTRAQ). A total of 98 proteins were overexpressed, while six proteins were underexpressed in CD34 + /CD38 − AML cells compared with their CD34 + /CD38 + counterparts. Proteins overexpressed in CD34 + /CD38 − AML cells included a number of proteins involved in DNA repair, cell cycle arrest, gland differentiation, antiapoptosis, adhesion, and drug resistance. Aberrant expression of CD82, a family of adhesion molecules, in CD34 + /CD38 − AML cells was noted in additional clinical samples ( n = 12) by flow cytometry. Importantly, down‐regulation of CD82 in CD34 + /CD38 − AML cells by a short hairpin RNA (shRNA) inhibited adhesion to fibronectin via up‐regulation of matrix metalloproteinases 9 (MMP9) and colony forming ability of these cells as assessed by transwell assay, real‐time RT‐PCR, and colony forming assay, respectively. Moreover, we found that down‐regulation of CD82 in CD34 + /CD38 − AML cells by an shRNA significantly impaired engraftment of these cells in severely immunocompromised mice. Taken together, aberrant expression of CD82 might play a role in adhesion of LSCs to bone marrow microenvironment and survival of LSCs. CD82 could be an attractive molecular target to eradicate LSCs.
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