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The deletion of chromosome 17p (del(17p)) is considered a crucial prognostic factor at the time of diagnosis in patients with multiple myeloma (MM). However, the impact of del(17p) on survival at different clonal sizes at relapse, as well as the patterns of clonal evolution between diagnosis and relapse and their prognostic value, has not been well described. To address these issues, we analyzed the interphase fluorescence in situ hybridization (iFISH) results of 995 newly diagnosed MM (NDMM) patients and 293 patients with MM at their first relapse. Among these patients, 197 had paired iFISH data at diagnosis and first relapse. Our analysis of paired iFISH revealed that a minor clone of del(17p) at relapse but not at diagnosis was associated with poor prognosis in MM (hazard ratio for median overall survival 1.64 vs. 1.44). Fifty-six and 12 patients developed one or more new cytogenetic abnormalities at relapse, mainly del(17p) and gain/amp(1q), respectively. We classified the patients into six groups based on the change patterns in the clonal size of del(17p) between the two time points. Patients who did not have del(17p) during follow-up showed the best outcomes, whereas those who acquired del(17p) during their disease course, experienced compromised survival (median overall survival: 61.3 vs. 49.4 months; hazard ratio =1.64; 95% confidence interval: 1.06-2.56; P<0.05). In conclusion, our data confirmed the adverse impact of a minor clone of del(17p) at relapse and highlighted the importance of designing optimal therapeutic strategies to eliminate high-risk cytogenetic abnormalities (clinicaltrials gov. identifier: NCT04645199).
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Mieloma Múltiplo , Humanos , Aberrações Cromossômicas , Hibridização in Situ Fluorescente , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , PrognósticoRESUMO
Prognostic significance of multiple immune antigens in multiple myeloma has been well established. However, a level of uncertainty remains regarding the intrinsic relationship between immunophenotypes and cytogenetic stability and precise risk stratification. To address these unresolved issues, we conducted a study involving 1389 patients enrolled in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Our results revealed that the correlation between antigen expression and cytogenetics is more prominent than cytopenia or organ dysfunction. Most immune antigens, apart from CD38, CD138, and CD81, exhibit significant associations with the incidence of at least one cytogenetic abnormality. In turn, we identified CD138-low/CD27-neg as specific adverse immunophenotypic profile, which remaining independent impact on progression-free survival (HR, 1.49; P = 0.007) and overall survival (HR, 1.77; P < 0.001) even in the context of cytogenetics. Importantly, CD138-low/CD27-neg profile was also associated with inferior survival after first relapse (P < 0.001). Moreover, the antigen expression profiles were not strictly similar when comparing diagnosis and relapse; in particular, the CD138-low/CD27-neg pattern was notably increased after disease progression (19.1 to 29.1%; P = 0.005). Overall, our study demonstrates that diverse immune profiles are strongly associated with cytogenetic stability, and a specific immunophenotype (CD138-low/CD27-neg) could effectively predict prognoses across different disease stages.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico , Aberrações Cromossômicas , Análise Citogenética , RecidivaRESUMO
BACKGROUND: Insulin resistance (IR) can lead to cellular metabolic disorders, activation of oxidative stress, and endothelial dysfunction, contributing to in-stent restenosis (ISR). The triglyceride-glucose index (TyG index), a new indicator reflecting IR, is extensively researched in the cardiovascular field. This study, through a meta-analysis, aimed to utilize a larger combined sample size and thereby enhance the overall test efficacy to explore the TyG index-ISR relationship. METHODS: A thorough search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane Library databases to find original papers and their references published between 1990 and January 2024. This search included both prospective and retrospective studies detailing the correlation between the TyG index and ISR in individuals with coronary heart disease (CHD). OUTCOMES: The five included articles comprised 3,912 participants, and the odds ratio (OR) extracted from each study was combined using the Inverse Variance method. Results showed that, in the context of CHD patients, each incremental unit in the TyG index, when treated as a continuous variable, corresponded to a 42% elevation in ISR risk (95% CI 1.26-1.59, I²=13%, p < 0.005). When analyzing the TyG index categorically, the results revealed a higher ISR risk in the highest TyG index group compared to the lowest group (OR: 1.69, 95% CI 1.32-2.17, I²=0). Additionally, in patients with chronic coronary syndrome (CCS), each unit increase in the TyG index, the risk of ISR in patients increased by 37% (95% CI 1.19-1.57, I²=0%, p < 0.005). This correlation was also observable in acute coronary syndrome (ACS) patients (OR:1.48, 95% CI 1.19-1.85, I²=0, p < 0.005). CONCLUSIONS: The TyG index, an economical and precise surrogate for IR, is significantly linked with ISR. Furthermore, this correlation is unaffected by the type of coronary heart disease.
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Biomarcadores , Glicemia , Doença da Artéria Coronariana , Reestenose Coronária , Resistência à Insulina , Intervenção Coronária Percutânea , Stents , Triglicerídeos , Humanos , Biomarcadores/sangue , Glicemia/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico , Reestenose Coronária/sangue , Reestenose Coronária/etiologia , Reestenose Coronária/diagnóstico , Reestenose Coronária/diagnóstico por imagem , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
To evaluate the antioxidant activity of flavonoids extracted from Chinese herb mulberry leaves (ML), flavonoids from mulberry leaves (FML) were extracted and purified by using ultrasonic-assisted enzymatic extraction and D101 macroporous resin. Using LC-MS/MS-Liquid Chromatography with tandem mass spectrometry analysis, hesperidin, rutoside, hyperoside, cyanidin-3-o-glucoside, myricitrin, cyanidin, and quercetin were identified, and NMR and UV were consistent with the verification of IR flavonoid characteristics. The antioxidant activity of FML has also been evaluated as well as the protective effect on 2,2 0-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress. The results showed that FML exhibited powerful antioxidant activity. Moreover, FML showed dose-dependent protection against AAPH-induced sheep erythrocytes' oxidative hemolysis. In the enzymatic antioxidant system, pretreatment with high FML maintained the balance of SOD, CAT, and GSH-Px; in the non-enzymatic antioxidant system, the content of MDA can be effectively reduced after FML treatment. This study provides a research basis for the development of natural products from mulberry leaves.
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Morus , Ovinos , Animais , Morus/química , Antioxidantes/química , Cromatografia Líquida , Fluormetolona/análise , Fluormetolona/farmacologia , Hemólise , Espectrometria de Massas em Tandem , Estresse Oxidativo , Eritrócitos , Flavonoides/química , Folhas de Planta/químicaRESUMO
This paper examines the risk contagion among international stock markets during the COVID-19 pandemic by using the realized volatility information from sixteen major stock markets in the world. The empirical evidence based on the connectedness methods of Diebold and Yilmaz (2012) and Baruník and Krehlík (2018) shows that the COVID-19 epidemic significantly increases the risk contagion effects in international stock markets. Besides, the risk spillovers from stock markets in European and American regions increase rapidly but those in Asian markets decrease obviously after the outbreak of COVID-19 pandemic. Finally, the risk contagion among international stock markets caused by the pandemic can last for about 6 to 8 months. These results provide important implications regarding to financial risk management and macroprudential design.
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Subtropical forests are important ecosystems globally due to their extensive role in carbon sequestration. Extreme climate events are known to introduce disturbances in the ecosystem that cause long-term changes in carbon balance and radiation reflectance. However, how these ecosystem function changes contribute to global warming in terms of radiative forcing (RF), especially in the years following a disturbance, still needs to be investigated. We studied an extreme snow event that occurred in a subtropical evergreen broadleaved forest in south-western China in 2015 and used 9 years (2011-2019) of net ecosystem CO2 exchange (NEE) and surface albedo (α) data to investigate the effect of the event on the ecosystem RF changes. In the year of the disturbance, leaf area index (LAI) declined by 40% and α by 32%. The annual NEE was -718â ±â 128 g C m-2 as a sink in the pre-disturbance years (2011-2014), but after the event, the sink strength dropped significantly by 76% (2015). Both the vegetation, indicated by LAI, and α recovered to pre-disturbance levels in the fourth post-disturbance year (2018). However, the NEE recovery lagged and occurred a year later in 2019, suggesting a more severe and lasting impact on the ecosystem carbon balance. Overall, the extreme event caused a positive (warming effect) net RF which was predominantly caused by changes in α (90%-93%) rather than those in NEE. This result suggests that, compared to the climate effect caused by forest carbon sequestration changes, the climate effect of α alterations can be more sensitive to vegetation damage induced by natural disturbances. Moreover, this study demonstrates the important role of vegetation recovery in driving canopy reflectance and ecosystem carbon balance during the post-disturbance period, which determines the ecosystem feedbacks to the climate change.
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Ecossistema , Neve , Carbono , Dióxido de Carbono , Mudança Climática , FlorestasRESUMO
In order to predict the effects of climate change on the global carbon cycle, it is crucial to understand the environmental factors that affect soil carbon storage in grasslands. In the present study, we attempted to explain the relationships between the distribution of soil carbon storage with climate, soil types, soil properties and topographical factors across different types of grasslands with different grazing regimes. We measured soil organic carbon in 92 locations at different soil depth increments, from 0 to 100â¯cm in southwestern China. Among soil types, brown earth soils (Luvisols) had the highest carbon storage with 19.5⯱â¯2.5â¯kgâ¯m-2, while chernozem soils had the lowest with 6.8⯱â¯1.2â¯kgâ¯m-2. Mean annual temperature and precipitation, exerted a significant, but, contrasting effects on soil carbon storage. Soil carbon storage increased as mean annual temperature decreased and as mean annual precipitation increased. Across different grassland types, the mean carbon storage for the top 100â¯cm varied from 7.6⯱â¯1.3â¯kgâ¯m-2 for temperate desert to 17.3⯱â¯2.9â¯kgâ¯m-2 for alpine meadow. Grazing/cutting regimes significantly affected soil carbon storage with lowest value (7.9⯱â¯1.5â¯kgâ¯m-2) recorded for cutting grass, while seasonal (11.4⯱â¯1.3â¯kgâ¯m-2) and year-long (12.2⯱â¯1.9â¯kgâ¯m-2) grazing increased carbon storage. The highest carbon storage was found in the completely ungrazed areas (16.7⯱â¯2.9â¯kgâ¯m-2). Climatic factors, along with soil types and topographical factors, controlled soil carbon density along a soil depth in grasslands. Environmental factors alone explained about 60% of the total variation in soil carbon storage. The actual depth-wise distribution of soil carbon contents was significantly influenced by the grazing intensity and topographical factors. Overall, policy-makers should focus on reducing the grazing intensity and land conversion for the sustainable management of grasslands and C sequestration.
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Carbono , Solo , Ciclo do Carbono , China , Pradaria , PoaceaeAssuntos
Aberrações Cromossômicas , Translocação Genética , Humanos , Prognóstico , Feminino , Masculino , Proteínas Proto-Oncogênicas c-maf/genética , Pessoa de Meia-Idade , Idoso , Adulto , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidadeRESUMO
Canopy temperature is a result of the canopy energy balance and is driven by climate conditions, plant architecture, and plant-controlled transpiration. Here, we evaluated canopy temperature in a rubber plantation (RP) and tropical rainforest (TR) in Xishuangbanna, southwestern China. An infrared temperature sensor was installed at each site to measure canopy temperature. In the dry season, the maximum differences (Tc - Ta) between canopy temperature (Tc) and air temperature (Ta) in the RP and TR were 2.6 and 0.1 K, respectively. In the rainy season, the maximum (Tc - Ta) values in the RP and TR were 1.0 and -1.1 K, respectively. There were consistent differences between the two forests, with the RP having higher (Tc - Ta) than the TR throughout the entire year. Infrared measurements of Tc can be used to calculate canopy stomatal conductance in both forests. The difference in (Tc - Ta) at three gc levels with increasing direct radiation in the RP was larger than in the TR, indicating that change in (Tc - Ta) in the RP was relatively sensitive to the degree of stomatal closure.
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Hevea , Floresta Úmida , Temperatura , Mudança Climática , Hevea/fisiologia , Raios Infravermelhos , Folhas de Planta/fisiologia , Transpiração Vegetal , Estações do Ano , Árvores/fisiologia , Clima TropicalRESUMO
Multiple myeloma (MM) is the most prevalent malignant monoclonal disease of plasma cells. There is mounting evidence that interactions with the bone marrow (BM) niche are essential for the differentiation, proliferation, survival, migration, and treatment resistance of myeloma cells. For this reason, gaining a deeper comprehension of how BM microenvironment compartments interact with myeloma cells may inspire new therapeutic ideas that enhance patient outcomes. This review will concentrate on the most recent findings regarding the mechanisms of interaction between microenvironment and MM and highlight research on treatment targeting the BM niche.
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Hypochlorite (ClO-), as the main component of widely used disinfectants in daily life, comes into closer contact with the human body, which can lead to a number of diseases. The high-performance method is increasingly needed to detect ClO- in our daily life. In this report, we successfully synthesized a FRET ratiometric fluorescent probe (NDAC) containing benzoxadiazole moieties and coumarin moieties bound via ethylenediamine. As expected, NDAC has excellent selectivity and anti-interference ability toward ClO-, and the ratio of fluorescence intensity (I471 nm/I533 nm) has a very good linear relationship with the concentration of ClO-, with a wide linear range (2.5-1750 µM) and low detection limit (0.887 µM). Furthermore, we have successfully applied it for the quantitative detection of ClO- in water samples in daily life. At the same time, there is a very clear change in the fluorescence color after the reaction of the NDAC with ClO-. The blue/green value (B/G) of this color change also shows a very good linear relationship to ClO- (5.0-1000 µM). Therefore, the NDAC has also been successfully used for test strip detection and quantitative detection of ClO- in actual samples through smartphone-based fluorescence image analysis, and this method can provide faster, more convenient and more accessible detection. In addition, NDAC sensors also have potential applications in the field of information anti-counterfeiting.
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Colorimetria , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Ácido Hipocloroso , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Ácido Hipocloroso/análise , Transferência Ressonante de Energia de Fluorescência/métodos , Colorimetria/métodos , Limite de Detecção , Humanos , Desinfetantes/análise , Cumarínicos/químicaRESUMO
Ozone (O3), a persistent pollutant, poses a significant health threat. However, research on its multigenerational toxicity remains limited. Leveraging the Drosophila model with its short lifespan and advanced genetic tools, we explored the effects of O3 exposure across three generations of fruit flies. The findings revealed that O3 disrupted motility, body weight, stress resistance, and oxidative stress in three generations of flies, with varying effects observed among them. Transcriptome analysis highlighted the disruption of glucose metabolism-related pathways, encompassing gluconeogenesis/glycolysis, galactose metabolism, and carbon metabolism. Hub genes were identified, and RT-qPCR results indicated that O3 decreased their transcription levels. Comparative analysis of their human orthologs was conducted using Comparative Toxicogenomics Database (CTD) and DisGeNET databases. These genes are linked to various metabolic diseases, including diabetes, hypoglycemia, and obesity. The trehalose content was reduced in F0 generation flies but increased in F1-F2 generations after O3 exposure. While the trehalase and glucose levels were decreased across F0-F2 generations. TAG synthesis-related genes were significantly upregulated in F0 generation flies but downregulated in F1-F2 generations. The expression patterns of lipolysis-related genes varied among the three generations of flies. Food intake was increased in F0 generation flies but decreased in F1-F2 generations. Moreover, TAG content was significantly elevated in F0 generation flies by O3 exposure, while it was reduced in F2 generation flies. These differential effects of O3 across three generations of flies suggest a metabolic reprogramming aimed at mitigating the damage caused by O3 to flies. The study affirms the viability of employing the Drosophila model to investigate the mechanisms underlying O3-induced glucose and lipid metabolism disorders while emphasizing the importance of studying the long-term health effects of O3 exposure. Moreover, this research highlights the Drosophila model as a viable tool for investigating the multigenerational effects of pollutants, particularly atmospheric pollutants.
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Bacillus Calmette Guerin (BCG) perfusion is widely used as cancer adjuvant therapy, in which macrophages play an important role. Novel macrophage activated associated protein 1 (NMAAP1), upregulated after BCG's activation, was proved to promote macrophage polarization to the M1 type. We found that BCG could stimulate mice BMDM to the M1 type and kill tumor cells. After the deletion of NMAAP1, the tumor volume of mice became larger, and the number of M1 type macrophages in the tumor decreased significantly. When macrophages were induced into the M1 type, aerobic glycolysis, the Warburg effect manifested in the increased uptake of glucose and the conversion of pyruvate to lactic acid. NMAAP1 could bind with IP3R and regulate macrophage polarization to the M1 type. However, the specific mechanism of how NMAAP1 regulates macrophage polarization towards the M1 type and plays an antitumor role must be clarified. NMAAP1 could promote the release of lactic acid and pyruvate, enhance the glycolysis of macrophages, and affect the expression of HIF-1α. After inhibition of glycolysis by 2-DG and lactic acid generation by FX11, the effects of NMAAP1 promoting macrophage polarization to the antitumor M1 type were weakened. Furthermore, NMAAP1 upregulated the expression of HIF-1α, which is associated with glycolysis. Moreover, the Ca2+/NF-κB pathway regulated HIF-1α expression by NMAAP1 in the macrophages. NMAAP1 promotes the polarization of macrophages towards the M1 type by affecting the Warburg effect stimulated by BCG.
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Vacina BCG , Macrófagos , Camundongos , Animais , Ativação de Macrófagos , Glicólise , Ácido Láctico/metabolismo , Piruvatos/farmacologiaRESUMO
Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a "two-step" process in the clonal size changes of gain/amp(1q) in MM.
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Hibridização in Situ Fluorescente , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Mieloma Múltiplo/mortalidade , Hibridização in Situ Fluorescente/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Cromossomos Humanos Par 1/genética , Adulto , Evolução Clonal/genética , Idoso de 80 Anos ou mais , Instabilidade Cromossômica , Aberrações Cromossômicas , Progressão da DoençaRESUMO
Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Epigênese Genética , Histonas/metabolismo , ADP-Ribosil Ciclase 1 , Células Matadoras NaturaisRESUMO
Residual normal plasma cells (NPCs), which compete with tumor plasma cells, play an important role in multiple myeloma. However, large-scale cohort studies investigating residual NPCs, especially at the minimal residual disease (MRD) phase, are currently lacking. In this study, we conducted a comprehensive investigation into the clinical significance of residual NPCs throughout the entire disease course in 1363 myeloma patients from the NICHE cohort (NCT04645199). Our results revealed that myeloma patients with high baseline NPCs ratio (≥5%) exhibited distinct indolent features, characterized by lower tumor burden, reduced frequencies of cytopenia, immunoparesis, and high-risk cytogenetics. Importantly, high residual NPCs ratio at diagnosis or relapse was independently associated with favorable survival. High absolute percentages of NPCs at undetectable MRD were related with superior clinical benefit and immune reconstitution. At MRD-positive phases, grouping based on NPCs ratio (<50%, 50-90%, ≥90%) demonstrated better risk stratification compared to residual tumor log levels. Based on the time-dependent NPCs ratio trend, we developed a dynamic MRD model that classifies patients into three groups with diverse longitudinal trends, leading to distinct prognoses. Collectively, residual NPCs serves not only as a valuable complementary biomarker for risk stratification but also provides valuable insights on reclassifications and kinetics of MRD.
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PURPOSE: We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma. EXPERIMENTAL DESIGN: A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10-5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated. RESULTS: Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26-7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12-0.52) and overall survival (HR, 0.16; 0.06-0.40). CONCLUSIONS: EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.
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Mieloma Múltiplo , Humanos , Neoplasia Residual/diagnóstico , Prognóstico , Sensibilidade e Especificidade , Citometria de Fluxo/métodosRESUMO
Multiple myeloma (MM) is an incurable cancer of the plasma cells. In the last twenty years, treatment strategies have evolved toward targeting MM cells-from the shotgun chemotherapy approach to the slightly more targeted approach of disrupting important MM molecular pathways to the immunotherapy approach that specifically targets MM cells based on protein expression. Antibody-drug conjugates (ADCs) are introduced as immunotherapeutic drugs which utilize an antibody to deliver cytotoxic agents to cancer cells distinctively. Recent investigations of ADCs for MM treatment focus on targeting B cell maturation antigen (BCMA), which regulates B cell proliferation, survival, maturation, and differentiation into plasma cells (PCs). Given its selective expression in malignant PCs, BCMA is one of the most promising targets in MM immunotherapy. Compared to other BCMA-targeting immunotherapies, ADCs have several benefits, such as lower price, shorter production period, fewer infusions, less dependence on the patient's immune system, and they are less likely to over-activate the immune system. In clinical trials, anti-BCMA ADCs have shown safety and remarkable response rates in patients with relapsed and refractory MM. Here, we review the properties and clinical applications of anti-BCMA ADC therapies and discuss the potential mechanisms of resistance and ways to overcome them.