Primary acute myeloid leukaemia blasts resistant to cytokine-induced differentiation to dendritic-like leukaemia cells can be forced to differentiate by the addition of bryostatin-1

Roddie, P. H.; Horton, Y. M.; Turner, M.

doi:10.1038/sj.leu.2402335

Cited by 30 publications

(25 citation statements)

References 18 publications

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“…AML cells naturally secrete interferon-g and IL-12 and it seems possible, at least in some cases, to differentiate blast cells in vitro into dendritic cells able to stimulate Induced costimulatory molecules by Ara-C in AML R Vereecque et al autologous CTL expansion, with specific activity against AML cells. [29][30][31][32][33][34] Expansion of specific CTL has also been reported using nonleukemic dendritic cells. 35 However, the optimal schedule to reinject these expanded CTL remained to be defined.…”

Section: Induced Costimulatory Molecules By Ara-c In Aml R Vereecque mentioning

confidence: 87%

Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

2004

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Chemotherapeutic drugs kill cancer cells mainly by direct cytotoxicity, but they might also induce a stronger host immune response by causing the tumor to produce costimulatory cell surface molecules like CD80. We previously reported that in myeloid leukemic cells, c-irradiation induced CD80 expression. In this study, we show that cytosine arabinoside (Ara-C), even at low doses, induced CD80 expression in vitro in mouse DA1-3b leukemic cells, by a mechanism that involved reactive oxygen species. In vivo experiments in the mouse DA1-3b/C3H whole-animal acute myeloid leukemia (AML) model showed that injection of Ara-C induced expression of CD80 and CD86, and decreased expression of B7-H1, indicating that chemotherapy can modify costimulatory molecule expression in vivo, in a way not necessarily observed in vitro. Mouse leukemic cells exposed in vivo to Ara-C were more susceptible to specific cytotoxic lymphocyte (CTL)-mediated killing. Ara-C also induced CD80 or CD86 expression in 14 of 21 primary cultured human AML samples. In humans being treated for AML, induction chemotherapy increased CD86 expression in the leukemic cells. These findings indicate possible synergistic strategies between CTL-based immunotherapy and chemotherapy for treatment. They also suggest an additional mechanism by which chemotherapy can eradicate AML blasts.

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Section: Induced Costimulatory Molecules By Ara-c In Aml R Vereecque mentioning

confidence: 87%

Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

2004

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“…Bryo-1 has been shown to activate human hematopoietic progenitor cell growth and promote T-cell activation (4,5). Another interest in Bryo-1 recently has been stimulated by the observation that Bryo-1 can facilitate the differentiation of myelogenous leukemic cells into monocytic or dendritic-like cells (6).…”

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confidence: 99%

Bryostatin-1 Enhances the Maturation and Antigen-Presenting Ability of Murine and Human Dendritic Cells

Hegde

Nagarkatti

2004

Cancer Research

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In this study, we investigated the effect of bryostatin-1 (Bryo-1), an antineoplastic agent, on dendritic cell (DC) maturation, activation, and functions. Murine bone marrow-derived DCs on culture with Bryo-1 alone, Bryo-1 ؉ calcium ionophore (CI), but not CI alone exhibited morphologic changes characteristic of mature DCs and expressed increased levels of CD40, CD80, and CD86. Moreover, Bryo-1 ؉ CI-treated DCs exhibited enhanced antigen-presenting ability to naive and antigenspecific T cells and alloreactive T cells. Bryo-1 ؉ CI-mediated activation of DCs involved protein kinase C (PKC), especially PKC-␣, -␦, and -, and addition of PKC inhibitors impaired their ability to activate T cells. Bryo-1 ؉ CI treatment of DCs did not activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, p38 MAPK, or stress-activated protein kinase/c-Jun NH 2 -terminal kinase pathways. Finally, treatment of DCs with Bryo-1 alone and Bryo-1 ؉ CI, but not CI alone, induced nuclear translocation of nuclear factor B as studied by confocal microscopy. DCs generated from human peripheral blood monocytes or from human cord blood CD34؉ hematopoietic stem cells, when cultured with Bryo-1 ؉ CI, also showed maturation and increased T-cell stimulatory activity. Bryo-1 ؉ CI was more potent in inducing maturation and activation of DCs when compared with other agents such as tumor necrosis factor ␣, lipopolysaccharide, or phorbol 12-myristate 13-acetate ؉ CI. Collectively, the current study shows for the first time that Bryo-1 alone or in combination with CI may promote the maturation of DCs and therefore may be useful in development of DC-based cancer immunotherapy.

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“…It could be shown that DC could be generated from every AML or MDS sample. 3, 6 Some approaches have been made to vaccinate AML patients with ex vivo differentiated leukemia-derived DC to enhance the patients' cellular immunity against naive blasts. 5 Using DC pulsed with HLA-A2-restricted WT1 peptides, CTLs could be generated that lysed specifically leukemic but not healthy CD34 þ cells, thereby yielding the proof of principle that DC presenting a leukemic antigen are mediators of an antileukemia directed cytotoxic reaction.…”

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confidence: 99%

“…The details of these clinical trials have been reported previously. [4][5][6] The diagnosis of ALL was made on morphologic evaluation of bone marrow or peripheral blood and was confirmed by central review. Gene expression profiling was performed using Qiagen RNA isolation (www.qiagen.com), amplification and hybridization to Affymetrix HG_U95Av2 oligonucleotide microarrays (www.affymetrix.com).…”

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confidence: 99%

Quantification of ex vivo generated dendritic cells (DC) and leukemia-derived DC contributes to estimate the quality of DC, to detect optimal DC-generating methods or to optimize DC-mediated T-cell-activation-procedures ex vivo or in vivo

Kremser

Loibl

et al. 2007

Leukemia

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Primary acute myeloid leukaemia blasts resistant to cytokine-induced differentiation to dendritic-like leukaemia cells can be forced to differentiate by the addition of bryostatin-1

Cited by 30 publications

References 18 publications

Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

Bryostatin-1 Enhances the Maturation and Antigen-Presenting Ability of Murine and Human Dendritic Cells

Quantification of ex vivo generated dendritic cells (DC) and leukemia-derived DC contributes to estimate the quality of DC, to detect optimal DC-generating methods or to optimize DC-mediated T-cell-activation-procedures ex vivo or in vivo

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