Plasma Level of Tumor Necrosis Factor-alpha (TNF-α) Correlates with Leukocytosis and Biological Features of Leukemic Cells, but not Treatment Response of Children with Acute Lymphoblastic Leukemia

Потапнев, Михаил Петрович; Petyovka, N. V.; Belevtsev, Mikhail; Savitskiy, Valery P.; Мигаль, Н. В.

doi:10.1080/1042819031000068025

Cited by 21 publications

(12 citation statements)

References 3 publications

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“…TNFα is highly expressed in different leukemia subtypes (Tsai et al, 2011;Volk et al, 2014). The plasma level of TNFα has been associated with leukocytosis in ALL, whereas in CML, TNFα enhances proliferation and survival of the malignant cells (Gallipoli et al, 2013;Potapnev et al, 2003). Placental growth factor (PlGF) is secreted by certain stromal cells in CML and was found to increase angiogenesis in the bone marrow and to promote CML proliferation and aggressiveness of the disease (Schmidt et al, 2011).…”

Section: Role Of the Bmm In Chemoresistancementioning

confidence: 99%

The bone marrow microenvironment in health and disease at a glance

Kumar

Godavarthy

Krause

2018

Journal of Cell Science

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The bone marrow microenvironment (BMM) is the 'domicile' of hematopoietic stem cells, as well as of malignant processes that can develop there. Multiple and complex interactions with the BMM influence hematopoietic stem cell (HSC) physiology, but also the pathophysiology of hematological malignancies. Reciprocally, hematological malignancies alter the BMM, in order to render it more hospitable for malignant progression. In this Cell Science at a Glance article and accompanying poster, we highlight concepts of the normal and malignant hematopoietic stem cell niches. We present the intricacies of the BMM in malignancy and provide approaches for targeting the interactions between malignant cells and their BMM. This is done in an effort to augment existing treatment strategies in the future.

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Section: Role Of the Bmm In Chemoresistancementioning

confidence: 99%

The bone marrow microenvironment in health and disease at a glance

Kumar

Godavarthy

Krause

2018

Journal of Cell Science

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“…In comparison to patients with plasma levels of TNF-α below the median value, they revealed that patients with plasma levels of TNF-α above the median value had considerably greater white blood cell and blast counts in peripheral blood. As a result, their findings show that an elevated TNF-α plasma level is a useful marker for assessing disease activity/progression, but not for predicting the prognosis of childhood ALL [ 16 ]. Drabko et al discovered that serum TNF-α levels were higher in children with ALL compared to the control group [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance

Verma¹,

Singh²,

Yadav³

et al. 2022

Cureus

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Introduction Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine that facilitates malignant cells in immune evasion, survival, and treatment resistance by generating a favorable milieu for them. It is shown to be ectopically produced by malignant/leukemic and immune cells in the tumor microenvironment, providing a tumor-supportive environment and playing an important part in the establishment and progression of malignant cells. It is linked to hyperleukocytosis, high blast count, and poor clinical outcomes in acute leukemia (AL). Considering the varied role and different expression patterns of tumor necrosis factor-alpha in acute leukemia and its clinical relevance, the present study was planned to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia and its correlation with disease outcome. The aim of this study was to monitor the level of tumor necrosis factor-alpha in patients with acute leukemia at the time of diagnosis and after induction chemotherapy. Material and methods The study included cases classified as acute leukemia based on morphological examination, bone marrow analysis, and flow cytometry. In all patients with acute leukemia (n = 90) and controls (n = 10), the serum tumor necrosis factor-alpha level was measured using a Diaclone Human ELISA kit (Diaclone, Besancon, France) (solid phase sandwich ELISA) at diagnosis and after induction chemotherapy. Results Tumor necrosis factor-alpha levels were substantially higher in T-acute lymphoblastic leukemia (T-ALL) cases, followed by acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL), at the time of diagnosis, compared to the control. A significant reduction in serum tumor necrosis factor-alpha level was seen in patients with acute leukemia after induction phase chemotherapy (P < 0.05). Tumor necrosis factor-alpha levels were considerably reduced (P < 0.001) in the majority of acute leukemia cases after the induction phase, while high tumor necrosis factor-alpha levels were positively correlated with incomplete remission status in the remaining cases. Conclusion Tumor necrosis factor-alpha is involved in the progression of acute leukemia and its relapse. High levels of tumor necrosis factor-alpha are linked to leukocytosis, high blast counts, and worse survival in patients with acute leukemia. Monitoring of tumor necrosis factor-alpha may be helpful in patients with acute leukemia in view of available antitumor necrosis factor-alpha therapy.

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“…TNF promotes the progression of several hematopoietic tumors by participating in several signaling pathways, including NF-κB, and PI3K/Akt [44,45]. It has been reported that TNF can be produced by various leukemia cells, including AML [36], ALL [46], CML [47], CLL [48], and so on. There was also evidence showing that TNF induced MMP9 expression or secretion in leukemia cells [49].…”

Section: Weighted Compound-target Bipartite Networkmentioning

confidence: 99%

Insights into the mechanism of Arnebia euchroma on leukemia via network pharmacology approach

Wang

et al. 2020

Preprint

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Background: Arnebia euchroma (A. euchroma), a traditional Chinese medicine (TCM) for the treatment of blood diseases. In recent years, more and more researches have been conducted on the anti-tumor effect of shikonin and its derivatives, the major active components of A. euchroma. However, the underlying mechanism of action (MoA) for all the ingredients of A. euchroma on leukemia has not been explored systematically.Methods: In this study, we tried to analyze the MoA of A. euchroma on leukemia via network pharmacology approach. Firstly, the chemical components and their concentrations in A. euchroma as well as leukemia-related targets were collected. Next, we predicted compound-target interactions (CTIs) via our balanced substructure-drug-target network-based inference (bSDTNBI) method. The known and predicted targets of A. euchroma and leukemia-related targets were merged together to construct A. euchroma-leukemia protein-protein interactions (PPIs) network. Then, weighted compound-target bipartite network was constructed according to combination of eight central attributes with concentrations information via Cytoscape. Additionally, molecular docking simulation was performed to determine the binding efficiency of compounds with targets.Results: A total of 65 components of A. euchroma were obtained and 27 of them with concentration information, which involved in 157 targets, 779 compound- target interactions (CTIs), including 129 known CTIs (KCTIs) and 650 predicted CTIs (PCTIs). Following the analysis of A. euchroma-leukemia PPI network, 37 targets were used to construct the weighted compound-target bipartite network and further KEGG pathway analysis. We found that A. euchroma candidate targets were significantly associated with several apoptosis and inflammation-related biological pathways, such as MAPK signaling pathway, PI3K-Akt signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathway. Moreover, molecular docking simulation demonstrated that there were 8 pairs of PCTIs had the strong binding free energy.Conclusions: This network pharmacology-based study considered the information of component concentration, in combination with molecular docking, deciphered that the efficacy of A. euchroma in the treatment of leukemia may be mainly attributed to 10 targets and 14 components, which were associated with inhibiting leukemia cell survival and inducing apoptosis, relieving inflammatory environment and inhibiting angiogenesis.

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Plasma Level of Tumor Necrosis Factor-alpha (TNF-α) Correlates with Leukocytosis and Biological Features of Leukemic Cells, but not Treatment Response of Children with Acute Lymphoblastic Leukemia

Cited by 21 publications

References 3 publications

The bone marrow microenvironment in health and disease at a glance

The bone marrow microenvironment in health and disease at a glance

Serum Tumor Necrosis Factor-Alpha Levels in Acute Leukemia and Its Prognostic Significance

Insights into the mechanism of Arnebia euchroma on leukemia via network pharmacology approach

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