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Blood Feb 2023
Topics: Humans; Multiple Myeloma; Neoplasms, Plasma Cell; Immunomodulating Agents
PubMed: 36757732
DOI: 10.1182/blood.2022018461 -
BMJ Case Reports Oct 2017Solitary plasmacytoma is a rare disorder comprising 5%-10% of all plasma cell neoplasms. Progression to multiple myeloma is the most common pattern of relapse....
Solitary plasmacytoma is a rare disorder comprising 5%-10% of all plasma cell neoplasms. Progression to multiple myeloma is the most common pattern of relapse. Appearance of new lesions without any systemic disease is the most unusual pattern of relapse seen in <2% cases. We present a case of a 46-year-old female who presented with features of third and seventh cranial nerve palsy, diagnosed with solitary plasmacytoma, with no evidence of any systemic disease. As per standard recommendations, the patient received radiotherapy to the local site. The patient developed relapse twice, at three sites, during the follow-up period. Investigations revealed no evidence of any systemic disease. In view of repeat relapses, the patient was started on immune modulatory agent. Two and half years after the last radiotherapy, the patient is symptom free with no evidence of any new lesion.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyclophosphamide; Diphosphonates; Disease Progression; Female; Femur; Humans; Magnetic Resonance Imaging; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Plasmacytoma; Thalidomide; Tomography, X-Ray Computed
PubMed: 29054949
DOI: 10.1136/bcr-2017-221780 -
American Society of Clinical Oncology... Apr 2022Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple...
Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple myeloma therapeutics has significantly changed over the last 2 decades, with disease remissions lasting much longer. The advent of modern-day induction regimens, usage of high-dose melphalan followed by autologous stem cell transplantation, and well-tolerated maintenance regimens has resulted in deeper and durable responses, with less frequent disease recurrences, and patients are living much longer. Moreover, the conventional testing for response assessments in multiple myeloma was developed at least 60 years earlier, and there was a clear need for more sensitive diagnostics to test measurable residual disease at deeper levels. Next-generation sequencing and next-generation flow cytometry are highly sensitive techniques that were refined over the last decade and have a sensitivity of 10 to 10 (1 cell per 100,000/1 million). More recently, immunotherapy strategies-including the cellular therapies-have allowed us to expand our ability to achieve and maintain measurable residual disease negativity even in the refractory setting. These advances have brought us much closer to a cure for multiple myeloma; clearly, it has become more realistically achievable, challenging the dogma of multiple myeloma as an incurable disease.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm, Residual; Transplantation, Autologous
PubMed: 35623025
DOI: 10.1200/EDBK_349603 -
International Journal of Molecular... Jan 2019Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes... (Review)
Review
Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has been demonstrated in angiogenesis associated with hematological tumors. In this review we focused on the role of mast cells in angiogenesis in human plasma cell malignancies. In this context, mast cells might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, permitting the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression.
Topics: Animals; Biomarkers; Bone Marrow; Cell Count; Cell Transformation, Neoplastic; Disease Susceptibility; Humans; Mast Cells; Multiple Myeloma; Neoplasms, Plasma Cell; Neovascularization, Pathologic; Plasmacytoma; Tumor Microenvironment
PubMed: 30678047
DOI: 10.3390/ijms20030481 -
American Journal of Transplantation :... May 2018Plasma cell diseases are a class of hematologic diseases that are sometimes present as preexisting diagnoses prior to organ transplantation, causative factors leading to... (Review)
Review
Plasma cell diseases are a class of hematologic diseases that are sometimes present as preexisting diagnoses prior to organ transplantation, causative factors leading to a need for organ transplantation, or may occur posttransplant as part of the spectrum of posttransplant lymphoproliferative disorders. Herein, we review the most common plasma cell diseases, both as coexisting with other causes of organ failure, but also as a primary underlying cause for organ failure. In many cases, treatment of the underlying clonal disease may be indicated before proceeding with organ transplant. This review aims to provide current and relevant data regarding the management of these conditions in the organ transplant patient, for transplant providers, and those who take care of these patients.
Topics: Graft Rejection; Humans; Multiple Myeloma; Neoplasms, Plasma Cell; Organ Transplantation; Plasma Cells; Risk Factors
PubMed: 29524307
DOI: 10.1111/ajt.14731 -
Blood Cancer Journal Sep 2021
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Disease Management; Humans; Immunotherapy, Adoptive; Lenalidomide; Multiple Myeloma; Stem Cell Transplantation
PubMed: 34535632
DOI: 10.1038/s41408-021-00550-z -
Experimental Hematology Aug 2015Multiple myeloma (MM) is a plasma-cell malignancy which remains incurable despite the recent emergence of multiple novel agents. Importantly, recent genetic and... (Review)
Review
Multiple myeloma (MM) is a plasma-cell malignancy which remains incurable despite the recent emergence of multiple novel agents. Importantly, recent genetic and molecular analyses have revealed the complexity and heterogeneity of this disease, highlighting the need for therapeutic strategies to eliminate all clones. Moreover, the bone marrow microenvironment, including stromal cells and immune cells, plays a central role in MM pathogenesis, promoting tumor cell growth, survival, and drug resistance. New classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and histone deacetylase inhibitors have shown remarkable efficacy; however, novel therapeutic approaches are still urgently needed to further improve patient outcomes. In this review, we discuss the recent advances and future strategies to ultimately develop MM therapies with curative potential.
Topics: Animals; Antineoplastic Agents; Bone Marrow; Humans; Multiple Myeloma; Tumor Microenvironment
PubMed: 26118499
DOI: 10.1016/j.exphem.2015.04.010 -
Blood Advances Mar 2023Spatial heterogeneity is a common phenomenon in metastatic solid tumors and an evolving concept in multiple myeloma (MM). The interplay between malignant plasma cells...
Spatial heterogeneity is a common phenomenon in metastatic solid tumors and an evolving concept in multiple myeloma (MM). The interplay between malignant plasma cells (PCs) and the microenvironment has not yet been analyzed in MM. For this purpose, we performed bone marrow aspirates and imaging-guided biopsies of corresponding lesions in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM) patients. PCs were isolated and subjected to whole-exome sequencing (WES). Non-PCs were studied with next-generation flow (NGF) and T-cell receptor sequencing (TCRseq) to analyze the connection between malignant and nonmalignant cells in the bone marrow and in lesions. Although we observed a strong overlap from WES, NGF, and TCRseq in patients with intramedullary disease, WES revealed significant spatial heterogeneity in patients with extramedullary disease. NGF showed significant immunosuppression in RRMM compared with NDMM as indicated by fewer myeloid dendritic cells, unswitched memory B cells, Th9 cells, and CD8 effector memory T cells but more natural killer and regulatory T cells. Additionally, fewer T-cell receptor (TCR) sequences were detected in RRMM compared with NDMM and healthy individuals. After induction therapy, TCR repertoire richness increased to levels of healthy individuals, and NGF showed more regulatory T cells and myeloid-derived suppressor cells, regardless of depth of response. Clinical significance of imaging-guided biopsies of lesions was demonstrated by detection of monoclonal PCs in patients without measurable residual disease (MRD) in aspirates from the iliac crest as well as identification of secondary primary malignancies in MRD- patients. Furthermore, site-specific clones with different drug susceptibilities and genetically defined high-risk features were detected by our workflow.
Topics: Humans; Multiple Myeloma; Bone Marrow; Plasma Cells; Neoplasms, Plasma Cell; Tumor Microenvironment
PubMed: 35868022
DOI: 10.1182/bloodadvances.2022007457 -
Frontiers in Immunology 2019B cell activation and differentiation yields plasma cells with high affinity antibodies to a given antigen in a time-frame that allows for host protection. Although the... (Review)
Review
B cell activation and differentiation yields plasma cells with high affinity antibodies to a given antigen in a time-frame that allows for host protection. Although the end product is most commonly humoral immunity, the rapid proliferation and somatic mutation of the B cell receptor also results in oncogenic mutations that cause B cell malignancies including plasma cell neoplasms such as multiple myeloma. Myeloma is the second most common hematological malignancy and results in over 100,000 deaths per year worldwide. The genetic alterations that occur in the germinal center, however, are not sufficient to cause myeloma, but rather impart cell proliferation potential on plasma cells, which are normally non-dividing. This pre-malignant state, referred to as monoclonal gammopathy of undetermined significance or MGUS, provides the opportunity for further genetic and epigenetic alterations eventually resulting in a progressive disease that becomes symptomatic. In this review, we will provide a brief history of clonal gammopathies and detail how some of the key discoveries were interwoven with the study of plasma cells. We will also review the genetic and epigenetic alterations discovered over the past 25 years, how these are instrumental to myeloma pathogenesis, and what these events teach us about myeloma and plasma cell biology. These data will be placed in the context of normal B cell development and differentiation and we will discuss how understanding the biology of plasma cells can lead to more effective therapies targeting multiple myeloma.
Topics: Animals; Cell Differentiation; Disease Progression; Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Plasma Cells
PubMed: 31231360
DOI: 10.3389/fimmu.2019.01121 -
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