Positive correlation between bone marrow mast cell density and ISS prognostic index in patients with multiple myeloma

Pappa, Constantina A.; Tsirakis, George; Roussou, Parascevi; Xekalou, Athina; Goulidaki, Nectaria; Konsolas, Ioannis; Alexandrakis, Michael G.; Stathopoulos, Efstathios N.

doi:10.1016/j.leukres.2013.09.012

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Increased mast cell density in the bone marrow of patients with MM is associated with angiogenesis, thus demonstrating the direct relationship of mast cells with the formation of new vessels to the tumor's blood supply [8,9].…”

Section: Introductionmentioning

confidence: 98%

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity

et al. 2015

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Multiple myeloma (MM) is a plasma cell neoplasm characterized by bone marrow infiltration from malignant plasma cells. Mast cells play an important role in inflammation and angiogenesis in malignant diseases. The aim of the study was to evaluate the mast cell density in bone marrow of untreated MM patients with markers of disease activity such as serum interleukin-6 (IL-6), B2M, and C-reactive protein (CRP), the grade of bone marrow infiltration, and the levels of produced paraprotein. We studied 86 newly diagnosed MM patients (46 males, 40 females, mean age 59 ± 13.7 years). Thirty of them reached plateau phase after chemotherapy and 20 healthy volunteers. According to the criteria of International Staging System (ISS) staging system, 23 patients had stage I, 30 had stage II, and 33 had stage III. The serum concentrations of CRP, B2M, and IL-6, and the mast cell density (MCD) values were significantly higher in MM patients' group (1.6 ± 1.8, 4.3 ± 2.9, 7.1 ± 5.1, and 9 ± 4.8), in comparison with those found in control group (0.4 ± 0.1, 1.5 ± 0.6, 1.1 ± 0.5, and 1.9 ± 0.7; p < 0.001 in all the cases). Significant differences were found between the grade of infiltration in bone marrow, and the paraprotein values in patients' serum before and after chemotherapy. Furthermore, there was a significant correlation between the MCD values and the prognostic markers CRP (r = 0.452, p < 0.0001), IL-6 (r = 0.475, p < 0.0001), bone marrow infiltration (r = 0.333, p < 0.0002), and serum paraprotein levels(r = 0.221, p < 0.04). High MCD values strengthen the hypothesis that mast cells participate in the pathogenesis of disease progression and may be used as an indicator of the disease activity.

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Section: Introductionmentioning

confidence: 98%

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity

et al. 2015

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“…And vascular endothelial growth factor (VEGF) released by mast cells causes an angiogenic response and promotes tumor angiogenesis, which plays vital biological roles in the growth and development of neoplastic disorders [46,47]. Several studies demonstrated that the degree of mast cell in ltration parallelled the severity of MM [48][49][50]. The correlations of the identi ed biomarkers with in ltrating immune cells were also calculated, showing signi cant interactions between hub genes and tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of potential biomarkers in cuproptosis from multiple myeloma

Zhu

Lin²,

2023

Preprint

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Background Multiple myeloma (MM) accounts for 1% of neoplastic diseases. Cuproptosis, a copper-triggered modality of mitochondrial cell death, might be a promising therapeutic target for cancer treatment. However, the role of cuproptosis-related genes (CRGs) in MM is not well characterized. Thus, we aimed to explore the diagnostic value of CRGs in MM and further illustrate the potential mechanism. Methods The differential expression of CRGs between MM and control samples was identified and validated in the GSE6477 and GSE47552 datasets downloaded from the Gene Expression Omnibus database. The least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms were applied to identify potential CRGs as diagnostic biomarkers for MM. Receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic performance of the biomarkers. Functional enrichment and correlation analyses were then conducted to figure out the underlying mechanisms. Results Based on the differentially expressed CRGs by the gene expression difference of samples, LASSO and SVM-RFE algorithms were used to identify a final number of two CRGs as potential biomarkers for MM: CDKN2A and GLS. The all area under the curve (AUC) values of the 2 marker gene-based logistic regression model were 0.933 and 0.886 in the training and validation cohort, respectively, indicating a good performance in predicting MM diagnosis. Functional enrichment and correlation analyses suggested that the biomarkers may promote MM cell tumorigenesis and survival by modulating the immune cells through its immune-related pathways. Conclusion Two CRGs (CDKN2A and GLS) were identified and validated as possible MM biomarkers, which developed a diagnostic potency and provided an insight for exploring the mechanism for MM.

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“…Multiple myeloma (MM) is the malignancy of neoplastic plasma cells infiltrating the bone marrow. Similar to lymphomas and leukemias, patients with MM have an infiltration of tryptase positive MCs in their BM, associated with increased neovascularization and angiogenesis (22). Cytokines such as IL-6, VEGF, TNF-a, B cell activating factor, and receptor activator of NF-kB ligand are elevated in MM (28).…”

Section: The Role Of Mast Cells In Myelomamentioning

confidence: 99%

Steering Mast Cells or Their Mediators as a Prospective Novel Therapeutic Approach for the Treatment of Hematological Malignancies

Mehtani

Puri

2021

Front. Oncol.

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Tumor cells require signaling and close interaction with their microenvironment for their survival and proliferation. In the recent years, Mast cells have earned a greater importance for their presence and role in cancers. It is known that mast cells are attracted towards tumor microenvironment by secreted soluble chemotactic factors. Mast cells seem to exert a pro-tumorigenic role in hematological malignancies with a few exceptions where they showed anti-cancerous role. This dual role of mast cells in tumor growth and survival may be dependent on the intrinsic characteristics of the particular tumor, differences in tumor microenvironment according to tumor type, and the interactions and heterogeneity of mediators released by mast cells in the tumor microenvironment. In many studies, Mast cells and their mediators have been shown to affect tumor survival and growth, prognosis, inflammation, tumor vascularization and angiogenesis. Modulating mast cell accumulation, viability, activity and mediator release patterns may thus be important in controlling these malignancies. In this review, we emphasize on the role of mast cells in lymphoid malignancies and discuss strategies for targeting and steering mast cells or their mediators as a potential therapeutic approach for the treatment of these malignancies.

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Positive correlation between bone marrow mast cell density and ISS prognostic index in patients with multiple myeloma

Cited by 9 publications

References 35 publications

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity

Genetic analysis of potential biomarkers in cuproptosis from multiple myeloma

Steering Mast Cells or Their Mediators as a Prospective Novel Therapeutic Approach for the Treatment of Hematological Malignancies

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