scholarly journals Influence of gut microbiome on multiple myeloma: friend or foe?

2020 ◽  
Vol 8 (1) ◽  
pp. e000576
Author(s):  
Nausheen Ahmed ◽  
Mahmoud Ghannoum ◽  
Molly Gallogly ◽  
Marcos de Lima ◽  
Ehsan Malek
Keyword(s):  
Multiple Myeloma ◽  
Gut Microbiome ◽  
Monoclonal Gammopathy ◽  
Potential Role ◽  
Plasma Cells ◽  
Innate Immune ◽  
Factors Affecting ◽  
Underlying Mechanisms ◽  
Over Time

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells, which typically evolves over time from its precursor, monoclonal gammopathy of undetermined significance. While the underlying mechanisms of this evolution remain elusive, immunomodulatory factors affecting the bone marrow (BM) microenvironment are suspected to play a role. There is an increasing evidence that the gut microbiome exerts an influence on its host’s adaptive and innate immune systems, inflammatory pathways and the BM microenvironment. Dysbiosis, therefore, may impact tumorigenesis in MM. This article gives an overview of potential mechanisms by which the microbiome may influence the pathogenesis of MM, MM patients’ responses to treatment and toxicities experienced by MM patients undergoing autologous transplant. It also discusses the potential role of the mycobiome in MM, a less studied component of the microbiome.

scholarly journals Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma

2020 ◽  
Vol 21 (20) ◽  
pp. 7539
Author(s):  
Amro M. Soliman ◽  
Teoh Seong Lin ◽  
Pasuk Mahakkanukrauh ◽  
Srijit Das
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Tumor Growth ◽  
Malignant Transformation ◽  
Bone Disease ◽  
Clinical Management ◽  
Potential Role ◽  
Plasma Cells ◽  
The Usa

Multiple myeloma (MM) is a cancerous bone disease characterized by malignant transformation of plasma cells in the bone marrow. MM is considered to be the second most common blood malignancy, with 20,000 new cases reported every year in the USA. Extensive research is currently enduring to validate diagnostic and therapeutic means to manage MM. microRNAs (miRNAs) were shown to be dysregulated in MM cases and to have a potential role in either progression or suppression of MM. Therefore, researchers investigated miRNAs levels in MM plasma cells and created tools to test their impact on tumor growth. In the present review, we discuss the most recently discovered miRNAs and their regulation in MM. Furthermore, we emphasized utilizing miRNAs as potential targets in the diagnosis, prognosis and treatment of MM, which can be useful for future clinical management.

scholarly journals The role of bone marrow microenvironment in the progression of multiple myeloma from monoclonal gammopathy of undetermined significance

2021 ◽  
Vol 16 (3) ◽  
pp. 26-32
Author(s):  
A. S. Khudovekova ◽  
Ya. A. Rudenko ◽  
A. E. Dorosevich
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Bone Marrow Microenvironment ◽  
Genetic Mutations ◽  
Microbiome Composition ◽  
The Impact ◽  
Undetermined Significance

Multiple myeloma is a tumor of plasma cells, one of the most common malignant blood diseases. It is preceded by a stage called monoclonal gammopathy of undetermined significance, from which true multiple myeloma develops in only a small percentage of cases. It was assumed that this process is associated with the accumulation of genetic mutations, but in recent years there is increasing evidence that the bone marrow microenvironment plays a key role in progression and that it can become a target for therapy that prevents the myeloma development. The review considers the role of mesenchymal stem cells, immune system cells, endotheliocytes, fibroblasts, adipocytes, osteoclasts and osteoblasts in multiple myeloma progression, as well as the impact of the sympathetic nervous system and microbiome composition.

scholarly journals MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3650
Author(s):  
Vanessa Desantis ◽  
Antonio Giovanni Solimando ◽  
Ilaria Saltarella ◽  
Antonio Sacco ◽  
Viviana Giustini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Hematological Malignancy ◽  
Bone Lesions ◽  
Step Process ◽  
Asymptomatic Phase ◽  
Undetermined Significance ◽  
Premalignant Conditions

Multiple myeloma (MM) is a hematological malignancy characterised by proliferation of clonal plasma cells (PCs) within the bone marrow (BM). Myelomagenesis is a multi-step process which goes from an asymptomatic phase, defined as monoclonal gammopathy of undetermined significance (MGUS), to a smouldering myeloma (SMM) stage, to a final active MM disease, characterised by hypercalcemia, renal failure, bone lesions anemia, and higher risk of infections. Overall, microRNAs (miRNAs) have shown to significantly impact on MM tumorigenesis, as a result of miRNA-dependent modulation of genes involved in pathways known to be crucial for MM pathogenesis and disease progression. We aim to revise the literature related to the role of miRNAs as potential diagnostic and prognostic biomarkers, thus highlighting their key role as novel players within the field of MM and related premalignant conditions.

scholarly journals RNase A Inhibits Formation of Neutrophil Extracellular Traps in Subarachnoid Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Anton Früh ◽  
Katharina Tielking ◽  
Felix Schoknecht ◽  
Shuheng Liu ◽  
Ulf C. Schneider ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Potential Role ◽  
Neutrophil Extracellular Traps ◽  
Brain Parenchyma ◽  
Rnase A ◽  
Innate Immune ◽  
Control Groups ◽  
Extracellular Traps ◽  
Over Time

Background: Subarachnoid hemorrhage (SAH) caused by rupture of an intracranial aneurysm, is a life-threatening emergency that is associated with substantial morbidity and mortality. Emerging evidence suggests involvement of the innate immune response in secondary brain injury, and a potential role of neutrophil extracellular traps (NETs) for SAH-associated neuroinflammation. In this study, we investigated the spatiotemporal patterns of NETs in SAH and the potential role of the RNase A (the bovine equivalent to human RNase 1) application on NET burden.Methods: A total number of n=81 male C57Bl/6 mice were operated utilizing a filament perforation model to induce SAH, and Sham operation was performed for the corresponding control groups. To confirm the bleeding and exclude stroke and intracerebral hemorrhage, the animals received MRI after 24h. Mice were treated with intravenous injection of RNase A (42μg/kg body weight) or saline solution for the control groups, respectively. Quadruple-immunofluorescence (IF) staining for cell nuclei (DAPI), F-actin (phalloidin), citrullinated H3, and neurons (NeuN) was analyzed by confocal imaging and used to quantify NET abundance in the subarachnoid space (SAS) and brain parenchyma. To quantify NETs in human SAH patients, cerebrospinal spinal fluid (CSF) and blood samples from day 1, 2, 7, and 14 after bleeding onset were analyzed for double-stranded DNA (dsDNA) via Sytox Green.Results: Neutrophil extracellular traps are released upon subarachnoid hemorrhage in the SAS on the ipsilateral bleeding site 24h after ictus. Over time, NETs showed progressive increase in the parenchyma on both ipsi- and contralateral site, peaking on day 14 in periventricular localization. In CSF and blood samples of patients with aneurysmal SAH, NETs also increased gradually over time with a peak on day 7. RNase application significantly reduced NET accumulation in basal, cortical, and periventricular areas.Conclusion: Neutrophil extracellular trap formation following SAH originates in the ipsilateral SAS of the bleeding site and spreads gradually over time to basal, cortical, and periventricular areas in the parenchyma within 14days. Intravenous RNase application abrogates NET burden significantly in the brain parenchyma, underpinning a potential role in modulation of the innate immune activation after SAH.

Cereblon Enhancer Methylation and IMiD Resistance in Multiple Myeloma

Blood ◽  
2021 ◽  
Author(s):  
Larissa Haertle ◽  
Santiago Barrio ◽  
Umair Munawar ◽  
Seungbin Han ◽  
Xiang Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
In Vitro Experiments ◽  
Immunomodulatory Drugs ◽  
Dna Hypermethylation ◽  
Direct Binding ◽  
Underlying Mechanisms ◽  
Over Time

Cereblon is the direct binding target of the immunomodulatory drugs that are commonly used to treat Multiple Myeloma, the second most frequent hematologic malignancy. Patients respond well to initial IMiD treatment but virtually all develop drug resistance over time with the underlying mechanisms poorly understood. We identified a yet undescribed DNA hypermethylation in an active intronic CRBN enhancer. Differential hypermethylation in this region was found increased in healthy plasma cells, but more pronounced in IMiD refractory MM. Methylation significantly correlated with decreased CRBN expression levels. DNTMi in vitro experiments induced CRBN enhancer demethylation and sensitizing effects on Lenalidomide treatment were observed in two MM cell lines. Thus, we provide first evidence that aberrant CRBN DNA methylation is a novel mechanism of IMiD resistance in Multiple Myeloma and may predict IMiD response prior treatment.

scholarly journals From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 446
Author(s):  
Kevin M. Rose ◽  
Stephanie J. Spada ◽  
Rebecca Broeckel ◽  
Kristin L. McNally ◽  
Vanessa M. Hirsch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Basis ◽  
Human Population ◽  
Rna Viruses ◽  
Arms Race ◽  
Innate Immune ◽  
Immunodeficiency Virus ◽  
Underlying Mechanisms ◽  
Hiv 1

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α. Although the molecular basis for its ability to restrict retroviruses is debated, it is currently accepted that TRIM5α forms higher-order assemblies around the incoming retroviral capsid that are not only disruptive for the virus lifecycle, but also trigger the activation of an antiviral state. More recently, it was discovered that TRIM5α restriction is broader than previously thought because it restricts not only the human retroelement LINE-1, but also the tick-borne flaviviruses, an emergent group of RNA viruses that have vastly different strategies for replication compared to retroviruses. This review focuses on the underlying mechanisms of TRIM5α-mediated restriction of retroelements and flaviviruses and how they differ from the more widely known ability of TRIM5α to restrict retroviruses.

Interleukin‐6 is expressed by plasma cells from patients with multiple myeloma and monoclonal gammopathy of undetermined significance

1998 ◽  
Vol 101 (2) ◽  
pp. 287-295 ◽  
Author(s):  
Hamdi I. A. Sati ◽  
Jane F. Apperley ◽  
Mike Greaves ◽  
John Lawry ◽  
Roger Gooding ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Interleukin 6 ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Undetermined Significance

scholarly journals Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them

2021 ◽  
Vol 22 (3) ◽  
pp. 1103
Author(s):  
Marco Cippitelli ◽  
Helena Stabile ◽  
Andrea Kosta ◽  
Sara Petillo ◽  
Angela Gismondi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Immunomodulatory Activity ◽  
Cancer Cell Growth ◽  
Cytotoxic Effects ◽  
Growth And Survival ◽  
Therapeutic Implications ◽  
Development And Differentiation ◽  
Innate Lymphocytes

The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.

Houttuynia cordatamodulates oral innate immune mediators: potential role of herbal plant on oral health

Oral Diseases ◽  
2015 ◽  
Vol 21 (4) ◽  
pp. 512-518 ◽  
Author(s):  
S Satthakarn ◽  
WO Chung ◽  
A Promsong ◽  
W Nittayananta
Keyword(s):  
Oral Health ◽  
Potential Role ◽  
Innate Immune ◽  
Immune Mediators ◽  
Herbal Plant

scholarly journals Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3582-3586 ◽  
Author(s):  
Sigurdur Y. Kristinsson ◽  
Thomas R. Fears ◽  
Gloria Gridley ◽  
Ingemar Turesson ◽  
Ulf-Henrik Mellqvist ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
First Year ◽  
Small Hospital ◽  
Entire Study ◽  
Crude Incidence ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Underlying Mechanisms ◽  
Undetermined Significance

Patients with multiple myeloma (MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT (crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively (crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P < .01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 (95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS (RR = 8.4; 95% CI, 5.7-12.2) and MM (RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM.

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