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Blood Advances Jan 2024
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive
PubMed: 38194242
DOI: 10.1182/bloodadvances.2023011659 -
International Journal of Molecular... Nov 2023Multiple myeloma (MM) is a hematological malignancy originated in the bone marrow and characterized by unhindered plasma cell proliferation that results in several... (Review)
Review
Multiple myeloma (MM) is a hematological malignancy originated in the bone marrow and characterized by unhindered plasma cell proliferation that results in several clinical manifestations. Although the main role of blood platelets lies in hemostasis and thrombosis, platelets also play a pivotal role in a number of other pathological conditions. Platelets are the less-explored components from the tumor microenvironment in MM. Although some studies have recently revealed that MM cells have the ability to activate platelets even in the premalignant stage, this phenomenon has not been widely investigated in MM. Moreover, thrombocytopenia, along with bleeding, is commonly observed in those patients. In this review, we discuss the hemostatic disturbances observed in MM patients and the dynamic interaction between platelets and myeloma cells, along with present and future potential avenues for the use of platelets for diagnostic and therapeutic purposes.
Topics: Humans; Blood Platelets; Multiple Myeloma; Hemorrhage; Hemostasis; Thrombosis; Cell Communication; Drug Delivery Systems; Tumor Microenvironment
PubMed: 37958838
DOI: 10.3390/ijms242115855 -
Journal of Cancer Research and Clinical... Aug 2023Multiple myeloma (MM) is the second most common hematological cancer that has no cure. Although currently there are several novel drugs, most MM patients experience drug... (Review)
Review
Multiple myeloma (MM) is the second most common hematological cancer that has no cure. Although currently there are several novel drugs, most MM patients experience drug resistance and disease relapse. The results of previous studies suggest that aberrant mitochondrial function may contribute to tumor progression and drug resistance. Mitochondrial DNA mutations and metabolic reprogramming have been reported in MM patients. Several preclinical and clinical studies have shown encouraging results of mitochondria-targeting therapy in MM patients. In this review, we have summarized our current understanding of mitochondrial biology in MM. More importantly, we have reviewed mitochondrial targeting strategies in MM treatment.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Mitochondria; Mutation
PubMed: 36928159
DOI: 10.1007/s00432-023-04672-8 -
Clinical Lymphoma, Myeloma & Leukemia Nov 2023We performed a systematic review of the literature investigating the demographic and insurance-related factors linked to disparities in multiple myeloma (MM) care... (Review)
Review
We performed a systematic review of the literature investigating the demographic and insurance-related factors linked to disparities in multiple myeloma (MM) care patterns in the United States from 2003 to 2021. Forty-six observational studies were included. Disparities in MM care patterns were reported based on patient race in 76% of studies (34 out of 45 that captured race as a study variable), ethnicity in 60% (12 out of 20), insurance in 77% (17 out of 22), and distance from treating facility, urbanicity, or geographic region in 62% (13 out of 21). A smaller proportion of studies identified disparities in MM care patterns based on other socioeconomic characteristics, with 36% (9 out of 25) identifying disparities based on income estimate or employment status and 43% (6 out of 14) based on language barrier or education-related factors. Sociodemographic characteristics are frequently associated with disparities in care for individuals diagnosed with MM. There is a need for further research regarding modifiable determinants to accessing care such as insurance plan design, patient out-of-pocket costs, preauthorization criteria, as well as social determinants of health. This information can be used to develop actionable strategies for reducing MM health disparities and enhancing timely and high-quality MM care.
Topics: Humans; United States; Multiple Myeloma; Ethnicity; Socioeconomic Factors; Income; Health Expenditures; Healthcare Disparities
PubMed: 37659966
DOI: 10.1016/j.clml.2023.08.008 -
Blood Cancer Journal Jul 2023There are disparities in outcomes for patients with multiple myeloma (MM). We evaluated the influence of sociodemographic factors on global disparities in outcomes for...
There are disparities in outcomes for patients with multiple myeloma (MM). We evaluated the influence of sociodemographic factors on global disparities in outcomes for patients with MM. This rapid evidence assessment (PROSPERO, CRD42021248461) followed PRISMA-P guidelines and used the PICOS framework. PubMed and Embase® were searched for articles in English from 2011 to 2021. The title, abstract, and full text of articles were screened according to inclusion/exclusion criteria. The sociodemographic factors assessed were age, sex, race/ethnicity, socioeconomic status, and geographic location. Outcomes were diagnosis, access to treatment, and patient outcomes. Of 84 articles included, 48 were US-based. Worldwide, increasing age and low socioeconomic status were associated with worse patient outcomes. In the US, men typically had worse outcomes than women, although women had poorer access to treatment, as did Black, Asian, and Hispanic patients. No consistent disparities due to sex were seen outside the US, and for most factors and outcomes, no consistent disparities could be identified globally. Too few studies examined disparities in diagnosis to draw firm conclusions. This first systematic analysis of health disparities in patients with MM identified specific populations affected, highlighting a need for additional research focused on assessing patterns, trends, and underlying drivers of disparities in MM.
Topics: Female; Humans; Male; Ethnicity; Hispanic or Latino; Meta-Analysis as Topic; Multiple Myeloma; Systematic Reviews as Topic; Healthcare Disparities; Health Status Disparities; Sex Factors; Black or African American; Asian
PubMed: 37460466
DOI: 10.1038/s41408-023-00877-9 -
The New England Journal of Medicine Oct 2023
Topics: Humans; Immunotherapy, Adoptive; Multiple Myeloma; Neoplasm Recurrence, Local; Receptors, Chimeric Antigen; Receptors, G-Protein-Coupled; T-Lymphocytes; Recurrence
PubMed: 37819961
DOI: 10.1056/NEJMc2308544 -
Cells Sep 2023G protein-coupled estrogen receptor 1 (GPER1) activation is emerging as a promising therapeutic strategy against several cancer types. While GPER targeting has been...
G protein-coupled estrogen receptor 1 (GPER1) activation is emerging as a promising therapeutic strategy against several cancer types. While GPER targeting has been widely studied in the context of solid tumors, its effect on hematological malignancies remains to be fully understood. Here, we show that GPER1 mRNA is down-regulated in plasma cells from overt multiple myeloma (MM) and plasma cell leukemia patients as compared to normal donors or pre-malignant conditions (monoclonal gammopathy of undetermined significance and smoldering MM); moreover, lower GPER1 expression associates with worse overall survival of MM patients. Using the clinically applicable GPER1-selective agonist G-1, we demonstrate that the pharmacological activation of GPER1 triggered in vitro anti-MM activity through apoptosis induction, also overcoming the protective effects exerted by bone marrow stromal cells. Noteworthy, G-1 treatment reduced in vivo MM growth in two distinct xenograft models, even bearing bortezomib-resistant MM cells. Mechanistically, G-1 upregulated the miR-29b oncosuppressive network, blunting an established miR-29b-Sp1 feedback loop operative in MM cells. Overall, this study highlights the druggability of GPER1 in MM, providing the first preclinical framework for further development of GPER1 agonists to treat this malignancy.
Topics: Humans; Multiple Myeloma; Hematologic Neoplasms; Smoldering Multiple Myeloma; Plasma Cells; MicroRNAs
PubMed: 37759449
DOI: 10.3390/cells12182226 -
Journal of Clinical Pathology Nov 2023Monoclonal gammopathy is a spectrum of disorders characterised by clonal proliferation of plasma cells or lymphocytes, which produce abnormal immunoglobulin or its...
Monoclonal gammopathy is a spectrum of disorders characterised by clonal proliferation of plasma cells or lymphocytes, which produce abnormal immunoglobulin or its components (monoclonal proteins). Monoclonal gammopathies are often categorised as low-tumour-burden diseases (eg, amyloid light chain (AL) amyloidosis), premalignant disorders (such as monoclonal gammopathy of undetermined significance and smouldering multiple myeloma), and malignancies (eg, multiple myeloma and Waldenström's macroglobulinaemia). Such diversity of concentration and structure makes monoclonal protein a challenging clonal marker. This article provides an overview on initial laboratory testing of monoclonal gammopathy to guide clinicians and laboratory professionals in the selection and interpretation of appropriate investigations.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Precancerous Conditions
PubMed: 37604683
DOI: 10.1136/jcp-2023-208774 -
Blood Feb 2024
Topics: Humans; Multiple Myeloma; Patients; Methylmethacrylates
PubMed: 38358852
DOI: 10.1182/blood.2023023293 -
Frontiers in Immunology 2023Subsets of patients diagnosed with a monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or multiple myeloma (MM), present with... (Review)
Review
Determination of the target of monoclonal immunoglobulins: a novel diagnostic tool for individualized MGUS therapy, and prevention and therapy of smoldering and multiple myeloma.
Subsets of patients diagnosed with a monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or multiple myeloma (MM), present with a monoclonal immunoglobulin (Ig) specific for an infectious pathogen, including hepatitis C and B viruses (HCV, HBV), and several . Such cases are likely initiated by infection, since in the context of HCV- or HBV-infected patients, antiviral therapy can lead to the disappearance of antigenic stimulation, control of clonal plasma cells, and reduced or suppressed monoclonal Ig production. Complete remission has been obtained with anti-HCV therapy in refractory MM with a HCV-specific monoclonal Ig, and antiviral treatments significantly improved the probability of survival of MM patients infected with HCV or HBV prior to the diagnosis of MM. Monoclonal Igs may also target glucolipids, particularly glucosylsphingosine (GlcSph), and GlcSph-reducing therapy can lead to complete remission in SMM and MM patients presenting with a GlcSph-specific monoclonal Ig. The present review describes the importance of determining the target of the monoclonal Ig of MGUS, SMM and MM patients, and discusses the efficacy of target-reducing treatments in the management of MGUS, SMM and MM cases who present with a monoclonal Ig reactive against a treatable infectious pathogen or GlcSph.
Topics: Humans; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma; Paraproteins; Antibodies, Monoclonal; Hepatitis C
PubMed: 38022528
DOI: 10.3389/fimmu.2023.1253363