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АнтиCD38 моноколональные антитела в множестве миеломы и за ее пределами: иммунотерапевтические механизмы, зрелость улик и клиническое позиционирование.

АнтиCD38 моноколональные антитела стали центральной иммунотерапевтической платформой во множестве миэломы, где они изменили курс лечения от рецидива или рефракторного заболевания, передней терапии, интенсификации технического обслуживания и минимального управления, ориентированного на остаточные заболевания. Их успех в многочисленных миеломах также стимулировал более широкое развитие в области иммуноглобулинового светового амилоида, отдельных гематологовых магнелез и юморальных иммунных расстройств. CD38 функционирует как как поверхностная мишень, так и как эктоэнзим, связанный с метаболизмом

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Anti-CD38 monoclonal antibodies have become a central immunotherapeutic platform in multiple myeloma, where they have reshaped treatment across relapsed or refractory disease, frontline therapy, maintenance intensification, and minimal residual disease-oriented management. Their success in multiple myeloma has also stimulated broader development in immunoglo…

Динамическая стратификация риска в мягкой миеломе: интеграция эволюционирующих биомаркеров с моделью 2/20/20.

Множественная миелома (SMM) является разнородным прекурсором с изменяющимся риском продвижения к миеломе (MM). Нынешние модели рисков основаны на базовых характеристиках, что ограничивает точность прогнозов. Мы стремились определить эволюционирующие факторы риска и интегрировать их в модель 2/20/20 для улучшения стратификации рисков. Мы проанализировали 323 пациента МРМ, диагностированных в соответствии с критериями ММРГ 2014 года в Центре им. Мемориала Слоана Кеттеринга (2002 - 2019 годы). В течение первого года, следующего за диагностикой, была проведена оценка измерений сериала М-протеина и…

Запоздалая прогрессивная многофукальная лейкоэнцефалопатия после теклистамб в множественной миеломе: продление периода инфекционного риска.

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… Features of reported progressive multifocal leukoencephalopathy cases in multiple myeloma. … Progressive multifocal leukoencephalopathy and BK virus-nephropathy with bispecific antibody therapy in multiple myeloma. Haematologica. 2026;111(1):431-435. 9. Hoeynck BW, Cohen AD, Stadtmauer EA, et al. Progressive multifocal leukoencephalopathy in multiple myeloma. …

Сокращенная специфическая реакция на патогенную Т ячейку с BCMA-Targeted T Cell-Enging Therapy to Multieloma.

ВВЕДЕНИЕ: Биогенное лечение антител (BsAb) может привести к увеличению числа инфекций у пациентов миэломы. Мы использовали ELISpot и цитометрию потока для проверки реакции T клеток на BCMA-CD3-диаграмму T-активиста (Bite) павурутамаб (PAV) и BCMA-выражающие клетки миэломы после внутривидовой культуры. Результаты: Снижение реакции на патогены было обнаружено в Т клетках, выращенных с PVV, но они уничтожили клетки миэломы. В исследовательском исследовании, в PBMC были обнаружены мягкие отзывы T-клеток, полученные от четырех пациентов миэломы, реагировавших на терапию BCMA. ЗАКЛЮЧЕНИЕ: Наше предв

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… Introduction Bispecific antibodies (BsAb) are effective in treatment of relapsed and refractory multiple myeloma, but can lead to adverse effects including increased rates and severity of infections, particularly where BCMA is targeted [ 1 ]. …

Analysis of early efficacy and immune reconstitution after autologous hematopoietic stem cell transplantation in multiple myeloma.

This retrospective study aimed to stress the advantages of autologous hematopoietic stem cell transplantation (auto-HSCT) in treating primary MM. Ninety-four MM patients who underwent initial parallel sequential auto-HSCT were selected. Data on efficacy (efficacy evaluation, renal function and hemoglobin recovery), immune reconstitution (B-cell subsets, immunoglobulin levels, T-cell subsets, NK cells, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR)) and hematopoietic reconstitution times were collected and analyzed. Whether in all selected patients or in groups R-ISS I

Multiple Myeloma Insights from Single-Cell Analysis: Clonal Evolution, the Microenvironment, Therapy Evasion, and Clinical Implications.

Multiple myeloma (MM) is a complex and heterogeneous hematologic malignancy characterized by clonal evolution, genetic instability, and interactions with a supportive tumor microenvironment. These factors contribute to treatment resistance, disease progression, and significant variability in clinical outcomes among patients. This review explores the mechanisms underlying MM progression, including the genetic and epigenetic changes that drive clonal evolution, the role of the bone marrow microenvironment in supporting tumor growth and immune evasion, and the impact of genomic instability. We hi…

[Establishment of a Bortezomib-Resistant Multiple Myeloma Xenotransplantation Mouse Model by Transplanting Primary Cells from Patients].

OBJECTIVE: To explore the construction method of a resistant multiple myeloma (MM) patient-derived xenotransplantation (PDX) model. METHODS: 1.0×107 MM patient-derived mononuclear cells (MNCs), 2.0×106 MM.1S cells and 2.0×106 NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdcscid Il2rgtm1/Bcgen (B-NDG) mice with a volume of 100 μl per mouse to establish mouse model. The morphologic, phenotypic, proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining, immunohistochemical staining (IHC), cell cycle analysis, flow cytometry an…

Significant attenuation of fully automated thrombin generation in newly diagnosed multiple myeloma patients after induction therapy.

Nearly 10% of newly diagnosed multiple myeloma (NDMM) patients develop a venous thromboembolism (VTE) episode during their disease course, despite current thromboprophylaxis strategies. Changes in hypercoagulability in these patients after treatment have been analyzed using the thrombin generation (TG) assay, the results being discrepant, probably due to the use of semi-automated techniques. This study aims to assess changes in TG measured by a fully automated analyzer. This prospective and multicentric study included NDMM patients from 8 centers (December 2018-September 2023). Fully automated…

Comprehensive bioinformatics analysis reveals key hub genes linked to prognosis in multiple myeloma with drug resistance.

Multiple myeloma (MM) is an incurable hematologic malignancy, with chemotherapy being the primary treatment. However, the development of drug resistance remains a major challenge. This study aimed to identify therapeutic targets associated with drug resistance in MM and assess their prognostic significance. Gene expression data from GSE82307, GSE146649, and GSE136725 were analyzed to identify differentially expressed genes (DEGs) using the "limma" and "RobustRankAggreg" R packages. Functional enrichment analysis and protein-protein interaction (PPI) network analysis were performed, with key ne…

Enhancer Extrachromosomal Circular DNA ANKRD28 Elicits Drug Resistance via POU2F2-Mediated Transcriptional Network in Multiple Myeloma.

Multiple myeloma (MM) remains an incurable disease primarily due to the emergence of drug resistance, and the underlying mechanisms remain unclear. Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes of both coding and non-coding regions. However, the role of non-coding eccDNA regions that serve as enhancers has been largely overlooked. Here, genome-wide profiling of serum eccDNAs from donors and MM patients who responded well or poorly to bortezomib-lenalidomide-dexamethasone (VRd) therapy is characterized. A high copy number of eccDNA ANKRD28 (eccANKRD28) predicts poor t…

Correction to "B-cell Maturation Antigen-Based Therapies Post-Talquetamab in Relapsed or Refractory Multiple Myeloma".

[This corrects the article DOI: 10.1002/jha2.896.].

Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma.

BACKGROUND/AIM: Multiple Myeloma (MM) is the second most common blood cancer, characterised by the accumulation of malignant plasma cells and the production of large amounts of a monoclonal immunoglobulin protein, in the bone marrow. The identification and progression/behaviour of molecular markers across stages remains a scientific challenge. This work aims to provide a holistic approach in the understanding of the disease progression through a computational approach, capable of characterising and distinguishing disease stages. MATERIALS AND METHODS: Stage-stratified MM transcriptomic datase…

A Nomogram for Predicting Progression-Free Survival in Primary Extramedullary Multiple Myeloma Using Routine Laboratory Variables.

INTRODUCTION: Extramedullary involvement in multiple myeloma represents aggressive disease, with clinical stratification of primary extramedullary disease (EMD) remaining a challenge. In this study, we aimed to develop a credible nomogram utilizing routine laboratory variables to predict individual survival for primary EMD patients. METHODS: We retrospectively analyzed a cohort of 60 primary EMD patients, from January 2006 to December 2022. Independent risk factors were identified and subsequently incorporated to generate a nomogram using the Cox proportional hazard regression model. Then, we…

Targeting GPRC5D With CAR-T Cells in Relapse/Refractory Multiple Myeloma: Case Report and Literature Review.

Multiple myeloma (MM) is the second most common hematologic malignancy, and patients with relapsed/refractory MM (RRMM) face limited treatment options and a poor prognosis. Recently, CAR-T cell therapy targeting G-protein-coupled receptor, class C group 5 member D (GPRC5D) has shown promising efficacy and safety in preclinical studies, offering new hope for patients with RRMM. We report the successful treatment of a 48-year-old female patient with relapsed/refractory nonsecretory MM. The patient had high-risk factors, including 1q21 amplification and TP53 deletion, and had relapsed after seven…

ATF4:p52 complex activates oncogenic enhancers in multiple myeloma via p300/CBP recruitment to regulate BACH1.

Multiple myeloma (MM) is a B-cell malignancy accounting for 20 % of all blood-associated cancers. MM patients with a poorer prognosis and high-risk stratification were previously observed to be causally linked to the constitutive activation of non-canonical NF-κB (ncNF-κB) pathway. Consistent with this, the ncNF-κB p52 transcription factor was earlier found to regulate the enhancer landscape of MM to potentiate oncogenic transcription. However, the mechanism by which aberrant p52 expression is involved in coordinating enhancer activity has not been well explored. In this study, we analysed H3K…

Genetic association between coffee consumption and multiple myeloma mediated by plasma metabolites: a Mendelian randomization study.

Background: Multiple myeloma (MM) is a hematologic malignancy closely associated with diets and metabolic disorders, showing an increasing incidence trend. Genome-wide association studies (GWAS) contribute to exploring the causal relationships between diets, metabolites, and MM, thereby revealing biological mechanisms underlying cancer progression. Methods: This study included large-scale GWAS data for two diets, four metabolomics, and MM. The two-sample Mendelian randomization (MR) analysis was conducted to assess causalities between these dietary patterns, metabolites, and MM. The MR analysi…