In vitro IL-12 treatment of peripheral blood mononuclear cells from patients with leukemia or myelodysplastic syndromes: increase in cytotoxicity and reduction in WT1 gene expression

Pan, Lei; Ohnishi, Kazunori; Zhang, W J; Yoshida, Hisao; Maksumova, Lola; Muratkhodjaev, Farkhad; Shigeno, Kazuyuki; Nakamura, Shuichi; Luo, Jinghui; Hao, Hong-Ling; Fujisawa, Shinya; Naito, Kensuke; Shinjo, Kaori; Takeshita, Akira; Ohno, Ryuzo

doi:10.1038/sj.leu.2401872

Cited by 5 publications

(2 citation statements)

References 25 publications

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“…More than a decade ago, IL-12p70 was shown to inhibit the angiogenic potential but not the survival or proliferation of AML cells ( 77 ) and to increase T-cell proliferation and cytotoxicity against leukemic cells in vitro ( 78 , 79 ). Multiple in vitro co-culture studies overexpressing IL-12p70 in dendritic cells have confirmed these findings ( 197 , 198 ) and paved the way for initial immunotherapies using genetically modified dendritic cells (phase 1 clinical trial NCT01734304) ( 199 ), thereby trying to avoid the toxicity of systemic administration of IL-12.…”

Section: Aml Inhibiting Cytokinesmentioning

confidence: 99%

The cytokine network in acute myeloid leukemia

2022

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Acute myeloid leukemia (AML) is a highly heterogeneous malignancy of the blood and bone marrow, characterized by clonal expansion of myeloid stem and progenitor cells and rapid disease progression. Chemotherapy has been the first-line treatment for AML for more than 30 years. Application of recent high-throughput next-generation sequencing technologies has revealed significant molecular heterogeneity to AML, which in turn has motivated efforts to develop new, targeted therapies. However, due to the high complexity of this disease, including multiple driver mutations and the coexistence of multiple competing tumorigenic clones, the successful incorporation of these new agents into clinical practice remains challenging. These continuing difficulties call for the identification of innovative therapeutic approaches that are effective for a larger cohort of AML patients. Recent studies suggest that chronic immune stimulation and aberrant cytokine signaling act as triggers for AML initiation and progression, facets of the disease which might be exploited as promising targets in AML treatment. However, despite the greater appreciation of cytokine profiles in AML, the exact functions of cytokines in AML pathogenesis are not fully understood. Therefore, unravelling the molecular basis of the complex cytokine networks in AML is a prerequisite to develop new therapeutic alternatives based on targeting cytokines and their receptors.

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Section: Aml Inhibiting Cytokinesmentioning

confidence: 99%

The cytokine network in acute myeloid leukemia

2022

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“…Indeed, priming of peripheral blood mononuclear cells (PBMC) with IL-12 increased their cytotoxicity against autologous leukemic blasts to almost normal levels and significantly reduced WT1 mRNA expression, used as a marker of residual leukemic burden, except in patients with overt, high-bulk AML. Thus, ex vivo priming of cytotoxic NK-T and NK cells could be used as a tool, targeting residual disease, following systemic chemotherapy [56].…”

Section: Nk Cell Abnormalitiesmentioning

confidence: 99%

Immune Dysregulation in Myelodysplastic Syndromes: Pathogenetic-Pathophysiologic Aspects and Clinical Consequences

Symeonidis¹,

Kouraklis-Symeonidis²

2016

Myelodysplastic Syndromes

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Myelodysplastic syndromes are clonal hematopoietic stem cell disorders, in which the immune system plays a substantial pathogenetic role. Patients manifest frequent infections, mainly attributed to neutropenia, but sometimes opportunistic pathogens are isolated in non-neutropenic patients. They also exhibit autoimmune diseases or syndromes with a background of immune activation and various abnormalities of Tlymphocytes, "-lymphocytes, and NK cells. The most typical profile includes reduced total T lymphocytes mainly CD + helper T-cells, resulting in decrease or inversion of the CD /CD cell ratio and impaired NK cell function. Many TH direction cytokines, and particularly sIL-R, IL-, and TNF-are usually found increased in the serum and bone marrow, which have been strongly associated with advanced disease, anemia, and other disease-related features. Clonal origin of lymphocytes has been confirmed only in few cases. Mixed lymphocyte cultures and genomic assays have shown severely impaired immunoregulatory abnormalities, probably induced by the hematopoietic cells. In a minority of patients, immune activation is capable to prevent or delay clonal expansion, but these patients have more profound hematopoietic impairment. Immunosuppressive treatment may not only relieve the autoimmune manifestations but also improve hematopoiesis. However, this kind of treatment is not well tolerated, is associated with severe infections, and in some cases may enhance "ML evolution.

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Molecular, Cytogenetic and Genetic Abnormalities in MDS and Secondary AML

Padua

McGlynn

2001

Cancer Treatment and Research

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In vitro IL-12 treatment of peripheral blood mononuclear cells from patients with leukemia or myelodysplastic syndromes: increase in cytotoxicity and reduction in WT1 gene expression

Cited by 5 publications

References 25 publications

The cytokine network in acute myeloid leukemia

The cytokine network in acute myeloid leukemia

Immune Dysregulation in Myelodysplastic Syndromes: Pathogenetic-Pathophysiologic Aspects and Clinical Consequences

Molecular, Cytogenetic and Genetic Abnormalities in MDS and Secondary AML

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