Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia

Hideto Tamura, Kazuo Dan, Koji Tamada, Kyoko Nakamura, Yumiko Shioi, Hideya Hyodo, Sheng Dian Wang, Haidong M Dong, Lieping Chen, Kiyoyuki Ogata

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5708-5717
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number16
DOIs
StatePublished - Aug 15 2005

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B7 Antigens
Acute Myeloid Leukemia
Survival
Myeloid Cells
Interleukin-4
Interleukin-10
Flow Cytometry
Research Design
Multivariate Analysis
Lymphocytes
T-Lymphocytes
Antibodies
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia. / Tamura, Hideto; Dan, Kazuo; Tamada, Koji; Nakamura, Kyoko; Shioi, Yumiko; Hyodo, Hideya; Wang, Sheng Dian; Dong, Haidong M; Chen, Lieping; Ogata, Kiyoyuki.

In: Clinical Cancer Research, Vol. 11, No. 16, 15.08.2005, p. 5708-5717.

Research output: Contribution to journalArticle

Tamura, Hideto ; Dan, Kazuo ; Tamada, Koji ; Nakamura, Kyoko ; Shioi, Yumiko ; Hyodo, Hideya ; Wang, Sheng Dian ; Dong, Haidong M ; Chen, Lieping ; Ogata, Kiyoyuki. / Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 16. pp. 5708-5717.
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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.",
author = "Hideto Tamura and Kazuo Dan and Koji Tamada and Kyoko Nakamura and Yumiko Shioi and Hideya Hyodo and Wang, {Sheng Dian} and Dong, {Haidong M} and Lieping Chen and Kiyoyuki Ogata",
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T1 - Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia

AU - Tamura, Hideto

AU - Dan, Kazuo

AU - Tamada, Koji

AU - Nakamura, Kyoko

AU - Shioi, Yumiko

AU - Hyodo, Hideya

AU - Wang, Sheng Dian

AU - Dong, Haidong M

AU - Chen, Lieping

AU - Ogata, Kiyoyuki

PY - 2005/8/15

Y1 - 2005/8/15

N2 - 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.

AB - 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.

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