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CD34 + /CD38 − acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells
Author(s) -
Nishioka Chie,
Ikezoe Takayuki,
Furihata Mutsuo,
Yang Jing,
Serada Satoshi,
Naka Tetsuji,
Nobumoto Atsuya,
Kataoka Sayo,
Tsuda Masayuki,
Udaka Keiko,
Yokoyama Akihito
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27904
Subject(s) - cd34 , cd38 , leukemia , stem cell , biology , microbiology and biotechnology , cancer research , cell adhesion molecule , bone marrow , immunology
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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