RRC ID 1477
著者 Tamura H, Dan K, Tamada K, Nakamura K, Shioi Y, Hyodo H, Wang SD, Dong H, Chen L, Ogata K.
タイトル Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia.
ジャーナル Clin Cancer Res
Abstract PURPOSE:The B7 family molecules have been shown to regulate immune responses in both positive and negative fashions. Their roles in the progression of human cancers, however, are not well established. The aim of this study was to examine whether leukemic cells of acute myeloid leukemia express functional B7 family molecules and, if so, whether such expression has any clinical significance.
EXPERIMENTAL DESIGN:The expression of four B7 family molecules, B7.1, B7.2, B7-H1, and B7-H2, on leukemic cells from acute myeloid leukemia patients was analyzed by flow cytometry. The function of the expressed molecules was examined by the allogeneic mixed lymphocyte-leukemic cell reaction, and their relationship to the clinical data and survival was analyzed.
RESULTS:Although B7.1 and B7-H1 expressions were rare, the cells from a substantial number of acute myeloid leukemia cases expressed B7.2 and B7-H2 molecules [mean percentages of B7.2- and B7-H2-positive cells were 28.9% (n = 58) and 15.3% (n = 59), respectively]. Patients in whom >25% of leukemic cells expressed B7-H2 had significantly shorter survival, and this B7-H2 positivity had the strongest prognostic value when B7-H2 and other prognostic factors were analyzed together by multivariate analysis (P = 0.0108). Furthermore, B7.2 expression was associated with hyperleukocytosis (P = 0.026). Consistent with this finding, acute myeloid leukemia cells expressing B7.2 and B7-H2 induced allogeneic CD4+ T cells to proliferate and secrete interleukin-4 and interleukin-10 in vitro, effects that were partially blocked by antibodies against B7.2 and B7-H2.
CONCLUSIONS:Our results indicate the expression of functional B7.2 and B7-H2 molecules, and these molecules may facilitate progression of acute myeloid leukemia.
巻・号 11(16)
ページ 5708-17
公開日 2005-8-15
DOI 10.1158/1078-0432.CCR-04-2672
PII 11/16/5708
PMID 16115907
MeSH Acute Disease Adult Aged Aged, 80 and over Analysis of Variance Antigens, CD B7-2 Antigen / analysis B7-2 Antigen / genetics* Bone Marrow Cells / metabolism Bone Marrow Cells / pathology CD4-Positive T-Lymphocytes / cytology CD4-Positive T-Lymphocytes / metabolism Cell Line, Tumor Cell Proliferation Coculture Techniques Culture Media, Conditioned / chemistry Culture Media, Conditioned / metabolism Female Flow Cytometry Gene Expression Regulation, Neoplastic HL-60 Cells Humans Inducible T-Cell Co-Stimulator Ligand Interferon-gamma / metabolism Interleukin-10 / metabolism Interleukin-2 / metabolism Interleukin-4 / metabolism Jurkat Cells K562 Cells Leukemia, Myeloid / genetics Leukemia, Myeloid / metabolism Leukemia, Myeloid / pathology* Male Middle Aged Prognosis Proteins / analysis Proteins / genetics* RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Survival Analysis U937 Cells
IF 10.107
引用数 71
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Jurkat(RCB0806) KG-1(RCB1166) BALL-1(RCB0256) OIH-1(RCB1290)