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Journal of Clinical Oncology : Official... Jan 2024
Topics: Humans; Multiple Myeloma
PubMed: 37847871
DOI: 10.1200/JCO.23.02017 -
Journal of Clinical Oncology : Official... Jul 2020
Topics: Disease Progression; Genomics; Humans; Multiple Myeloma; Smoldering Multiple Myeloma
PubMed: 32463739
DOI: 10.1200/JCO.20.00875 -
Leukemia Nov 2020Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by clonal proliferation of plasma cells and a heterogenous genomic landscape. Copy number and... (Review)
Review
Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by clonal proliferation of plasma cells and a heterogenous genomic landscape. Copy number and structural changes due to chromosomal instability (CIN) are common features of MM. In this review, we describe how primary and secondary genetic events caused by CIN can contribute to increased instability across the genome of malignant plasma cells; with a focus on specific driver genomic events, and how they interfere with cell-cycle checkpoints, to prompt accelerated proliferation. We also provide insight into other forms of CIN, such as chromothripsis and chromoplexy. We evaluate how the tumor microenvironment can contribute to a further increase in chromosomal instability in myeloma cells. Lastly, we highlight the role of certain mutational signatures in leading to high mutation rate and genome instability in certain MM patients. We suggest that assessing CIN in MM and its precursors states may help improve predicting the risk of progression to symptomatic disease and relapse and identifying future therapeutic targets.
Topics: Animals; Chromosomal Instability; DNA Copy Number Variations; Genetic Association Studies; Genetic Predisposition to Disease; Genomic Instability; Humans; Multiple Myeloma; Mutation; Tumor Microenvironment
PubMed: 32651540
DOI: 10.1038/s41375-020-0921-y -
European Journal of Haematology Oct 2020To evaluate changes in diagnostic and therapeutic approach in multiple myeloma among Norwegian hematologists in the current decade.
OBJECTIVE
To evaluate changes in diagnostic and therapeutic approach in multiple myeloma among Norwegian hematologists in the current decade.
METHODS
This nationwide study in Norway is based on results of surveys conducted among professionally active hematologists from 2013 to 2019. Every year, respondents participating in the survey suggested treatment regimens used in typical clinical situations in patients with multiple myeloma, as well as diagnostic routines.
RESULTS
The use of regimens containing alkylators and thalidomide was common at the beginning of the studied period. Later, lenalidomide became the most preferred treatment in most first-line patients. Bortezomib maintained a stable position in the treatment of myeloma in patients with renal insufficiency. The lenalidomide, bortezomib, and dexamethasone combination became the preferred frontline triplet for transplant-ineligible patients and induction therapy before transplant. Nowadays, the relapse after lenalidomide-based treatment is managed using both bortezomib-based therapies and combinations with the newest agents. Together with the therapeutic landscape, the use of diagnostic criteria and workup as well as supportive care changed in the period influenced by local and international guidelines and recommendations.
CONCLUSION
Norwegian hematologists gradually adopt new clinical concepts, guidelines, and recommendations in their practice.
Topics: Clinical Decision-Making; Combined Modality Therapy; Disease Management; Female; Health Care Surveys; Humans; Male; Multiple Myeloma; Norway; Outcome Assessment, Health Care; Physicians; Practice Patterns, Physicians'; Treatment Outcome
PubMed: 32557833
DOI: 10.1111/ejh.13464 -
Mayo Clinic Proceedings Feb 2024
Topics: Humans; Multiple Myeloma; Scleromyxedema; Paraproteinemias; Skin
PubMed: 38309938
DOI: 10.1016/j.mayocp.2023.08.022 -
Technology in Cancer Research &... 2023Multiple myeloma (MM) produces clonal plasma cells and aberrant monoclonal antibody accumulation in patients' bone marrow (BM). Around 1% of all cancers and 13% of... (Review)
Review
Multiple myeloma (MM) produces clonal plasma cells and aberrant monoclonal antibody accumulation in patients' bone marrow (BM). Around 1% of all cancers and 13% of hematological malignancies are caused by MM, making it one of the most common types of cancer. Diagnostic and therapeutic methods for managing MM are currently undergoing extensive research. MicroRNAs (miRNAs) are short noncoding RNAs that reduce or inhibit the translation of their target mRNA after transcription. Because miRNAs play an influential role in how myeloma develops, resources, and becomes resistant to drugs, miRNA signatures may be used to diagnose, do prognosis, and treat the myeloma response. Consequently, researchers have investigated the levels of miRNA in plasma cells from MM patients and developed tools to test whether they directly impacted tumor growth. This review discusses the latest discoveries in miRNA science and their role in the development of MM. We also emphasize the potential applications of miRNAs to diagnose, prognosticate, and treat MM in the future.
Topics: Humans; MicroRNAs; Multiple Myeloma; Prognosis; Bone Marrow; Drug Resistance; Gene Expression Regulation, Neoplastic
PubMed: 37728167
DOI: 10.1177/15330338231202391 -
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 -
Gaceta Medica de Mexico 2020To identify this increasingly common pathology, known as multiple myeloma (MM), it is necessary to refer to the specific factors that characterize it; to this end, the...
To identify this increasingly common pathology, known as multiple myeloma (MM), it is necessary to refer to the specific factors that characterize it; to this end, the classic criteria known as CRAB (hyperkalemia, renal failure, anemia, and lytic lesions) are available, in which renal failure is one of the most frequent complications. Recently, three indisputable biomarkers have been described for the diagnostic support for MM, which are: more than 10% of clonal plasma cells in bone marrow or, a biopsy that corroborates the presence of a plasmacytoma, light chain ratio ≥ 100 mg/dL and more than one focal lesion on magnetic resonance imaging. A differential diagnosis for plasma cell leukemia, solitary bone plasmacytoma, and extramedullary plasmacytoma should always be considered. Being this an incurable disease, a lot of research has been done regarding its therapeutic management, whose main objective is the disappearance of plasma cells and the patient clinical improvement. Melphalan was the first drug that showed a benefit in 1958 and afterward, with the addition of a steroid as a second drug, it was possible to improve response rates. Subsequently, different molecules were studied, forming multiple combinations, and achieving better rates of overall survival and progression-free survival. Years later, with the arrival of proteasome inhibitors such as bortezomib, and immunomodulators such as thalidomide and lenalidomide, an important turnaround in the disease has been seen, as deeper responses, more prolonged remissions, and improvement in the quality of life of patients have been achieved. This consensus has the purpose of integrating a group of Mexican specialists and promoting the updating of this pathology.
Topics: Algorithms; Humans; Mexico; Multiple Myeloma
PubMed: 33103663
DOI: 10.24875/GMM.M20000393 -
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 -
Hematology/oncology Clinics of North... Apr 2024Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal... (Review)
Review
Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal failure, and lytic Bone disease. It is preceded, often for decades, by a relatively stable monoclonal gammopathy lacking these clinical and malignant features. Both conditions are characterized by the presence of types of immunoglobulin heavy gene translocations that dysregulate a cyclin D family gene on 11q13 (CCND1), 6p21 (CCND3), or 12q11 (CCND2), a maf family gene on 16q23 (MAF), 20q11 (MAFB), or 8q24 (MAFA), or NSD2/FGFR3 on 4p16, or the presence of hyperdiploidy. Subsequent loss of function of tumor suppressor genes and mutations activating MYC, RAS, NFkB, and cell cycle pathways are associated with the progression to malignant disease.
Topics: Humans; Multiple Myeloma; Translocation, Genetic; Gene Rearrangement; Mutation; Monoclonal Gammopathy of Undetermined Significance; Immunoglobulins
PubMed: 38199896
DOI: 10.1016/j.hoc.2023.12.010