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Current Oncology Reports Jul 2024Plasma Cell Leukemia (PCL) is a very rare and highly aggressive form of plasma cell dyscrasia. This review seeks to evaluate the outcomes of PCL in the context of... (Review)
Review
PURPOSEOF REVIEW
Plasma Cell Leukemia (PCL) is a very rare and highly aggressive form of plasma cell dyscrasia. This review seeks to evaluate the outcomes of PCL in the context of combination novel agent therapy and stem cell transplant (SCT) protocols.
RECENT FINDINGS
The diagnostic criteria for PCL have now evolved to include patients with 5% circulating PC. While management remains challenging, the incorporation of novel agent-based induction regimen has significantly improved early mortality and reduced attrition of patients proceeding to SCT. In recent prospective clinical trials, patients with PCL demonstrated an overall response rates of 69% to 86%, with progression-free and overall survival ranging from 13.8 to 15.5 months and 24.8 to 36.3 months, respectively. B-cell lymphoma 2 (BCL2) inhibitors, such as venetoclax present a targeted intervention opportunity for patients with PCL with t(11;14). Dedicated clinical trials tailored to PCL are crucial, integrating newer therapies in the frontline setting to further optimize responses and enhance overall outcomes.
PubMed: 38954316
DOI: 10.1007/s11912-024-01563-0 -
Bulletin of Experimental Biology and... Jul 2024Coronary heart disease (CHD) is related to aberrant aggregation of immune cells in the plaques. This study focused on identification of abnormal T cell subtypes and...
Coronary heart disease (CHD) is related to aberrant aggregation of immune cells in the plaques. This study focused on identification of abnormal T cell subtypes and inflammatory factors in CHD patients. To this end, the subtypes of T cells in peripheral blood of CHD patients (n=141) and healthy controls (n=46) were analyzed by flow cytometry. Plasma concentrations of cytokines were analyzed by multiplex assay. It was shown that the number of T helper cells producing granulocyte-macrophage CSF (GM-CSF) was higher in CHD patients in comparison with healthy controls. In addition, the fractions of Th1 and Th17 cells as well as the levels of IL-4, IL-5, IL-6, and IL-10 in CHD patients also surpassed the control values (p<0.05). However, the level of GM-CSF was insignificantly lower in CHD patients. Thus, we revealed a relationship between the number of T cells producing GM-CSF and the severity of CHD. Our results can be used to develop new potential biomarkers for CHD detection.
PubMed: 38954298
DOI: 10.1007/s10517-024-06122-y -
Methods in Molecular Biology (Clifton,... 2024Activation processes at the plasma membrane have been studied with life-cell imaging using GFP fused to a protein that binds to a component of the activation process. In...
Activation processes at the plasma membrane have been studied with life-cell imaging using GFP fused to a protein that binds to a component of the activation process. In this way, PIP3 formation has been monitored with CRAC-GFP, Ras-GTP with RBD-Raf-GFP, and Rap-GTP with Ral-GDS-GFP. The fluorescent sensors translocate from the cytoplasm to the plasma membrane upon activation of the process. Although this translocation assay can provide very impressive images and movies, the method is not very sensitive, and amount of GFP-sensor at the plasma membrane is not linear with the amount of activator. The fluorescence in pixels at the cell boundary is partly coming from the GFP-sensor that is bound to the activated membrane and partly from unbound GFP-sensor in the cytosolic volume of that boundary pixel. The variable and unknown amount of cytosol in boundary pixels causes the low sensitivity and nonlinearity of the GFP-translocation assay. Here we describe a method in which the GFP-sensor is co-expressed with cytosolic-RFP. For each boundary pixels, the RFP fluorescence is used to determine the amount of cytosol of that pixel and is subtracted from the GFP fluorescence of that pixel yielding the amount of GFP-sensor that is specifically associated with the plasma membrane in that pixel. This GRminusRD method using GFP-sensor/RFP is at least tenfold more sensitive, more reproducible, and linear with activator compared to GFP-sensor alone.
Topics: Cell Membrane; Green Fluorescent Proteins; Humans; Luminescent Proteins; Protein Transport; Microscopy, Fluorescence; Cytosol; Animals
PubMed: 38954203
DOI: 10.1007/978-1-0716-3894-1_10 -
Methods in Molecular Biology (Clifton,... 2024Eukaryotic cells have been constantly challenged throughout their evolution by pathogens, mechanical stresses, or toxic compounds that induce plasma membrane (PM) or...
Eukaryotic cells have been constantly challenged throughout their evolution by pathogens, mechanical stresses, or toxic compounds that induce plasma membrane (PM) or endolysosomal membrane damage. The survival of the wounded cells depends on damage detection and repair machineries that are evolutionary conserved between protozoan, plants, and animals. We use the social amoeba Dictyostelium discoideum as a model system to study bacteria, mechanical or sterile membrane damage that allows us to identify and monitor factors involved in PM, endolysosomal damage response (ELDR), and endolysosomal homeostasis. Importantly, the sterile damage techniques presented here homogenously affect cell populations, which allows to phenotype mutant strains and quantify various aspects of cell fitness using live cell microscopy. This is instrumental to functionally assess genes involved in the repair of damaged plasma membrane or intracellular compartments and the degradation of extensively damaged compartments. Here, we describe how to inflict sterile PM or endolysosomal membrane damage, how to monitor the cell-intrinsic response to damage, and how to proxy proton leakage from damaged acidic compartments and quantify cell viability.
PubMed: 38954196
DOI: 10.1007/978-1-0716-3894-1_3 -
Pediatric Cardiology Jul 2024Plasma exchange is an effective treatment for Kawasaki disease (KD), suggesting that plasma from patients with KD bears its causative agents. The aim of this study was...
Plasma exchange is an effective treatment for Kawasaki disease (KD), suggesting that plasma from patients with KD bears its causative agents. The aim of this study was to use mass spectrometry to identify candidate agents in patient sera. Serum samples were obtained from 17 KD patients. In six patients, samples were collected in each of three phases: the acute phase prior to acetylsalicylic acid (ASA) and intravenous immunoglobulin administration (Phase A1), the remission phase with ASA (Phase A2), and the remission phase without any medication (Phase A3). Sera from the remaining 11 patients were collected during Phases A1 and A2. The study also included two age- and gender-matched control groups, one with eight afebrile children and one with eight febrile children diagnosed with infectious disease. Patients in Phase A1 and febrile controls did not differ in body temperature, white blood cell counts, or C-reactive protein levels. Mass spectrometry analysis revealed that the intensity levels of m/z 9416, identified as apolipoprotein CIII (Apo CIII), were lower in Phase A1 samples compared with samples from patients in Phases A2 and A3, and from febrile controls (all comparisons, p < 0.01). Serum Apo CIII levels were also lower in Phase A1 samples compared with samples from Phase A2 patients and afebrile controls (both p < 0.01), but samples from patients in Phase A2 did not differ significantly from those of the afebrile controls (p = 0.55). This study demonstrated that serum Apo CIII level was decreased in the acute phase of KD.
PubMed: 38953952
DOI: 10.1007/s00246-024-03546-1 -
Minerva Obstetrics and Gynecology Jul 2024Fetal aneuploidies, including trisomies 21, 13, and 18, represent a significant issue in prenatal care. The advent of non-invasive prenatal testing (NIPT) through the...
BACKGROUND
Fetal aneuploidies, including trisomies 21, 13, and 18, represent a significant issue in prenatal care. The advent of non-invasive prenatal testing (NIPT) through the detection of cell-free DNA (cf-DNA) in maternal blood has modified screening for chromosomal abnormalities. This study evaluates NIPT adherence among pregnant of different ethnicities, addressing potential disparities in prenatal care.
METHODS
This was a retrospective, single-center study conducted at a tertiary care university hospital in Italy between March 31, 2021, and September 30, 2022. Participants were categorized by ethnicity (Asian/Pacific islander, Black, Latina, White, Middle Eastern). Maternal demographic characteristics and prenatal test data were recorded. Comparative analyses were executed utilizing a One-Way Analysis of Variance (ANOVA) Test, augmented by Tukey's honestly significant difference test for post-hoc evaluation. Statistical significance was denoted by a P value (P)<0.05. A multivariate analysis through a multinomial regression model was conducted for the results to detect potential bias.
RESULTS
Six hundred seventeen pregnancies were included: 418 White, 105 Asian/Pacific islander, 46 Black, 40 Latina, and 8 Middle Eastern. Maternal age showed no significant variation. Black ethnicity had higher prepregnancy Body Mass Index (BMI; mean: 27.5 kg/m±SD: 5.92, P=0.02), while Asian and White pregnancies had higher nulliparity rates (63.8% and 70.8%). Black ethnicity had no NIPT uptake (0.00%). Asian/Pacific islander and Latina pregnant had lower NIPT utilization (9.5% and 7.5%, P<0.001). White ethnicity had a higher NIPT rate (27.5%). In the NIPT group, 8.9% of White and 12.5% of Middle Eastern pregnancies chose cf-DNA without a prior first-trimester ultrasound test. Considering the first-trimester screening, 30.4% of Black pregnancies had nuchal translucency, while 17.4% combined it with beta-human chorionic gonadotrophin (β-hCG) and associated plasma protein-A (PAPP-A; P<0.001). White pregnancies had high adherence: 74.6% had nuchal translucency and 53.8% had a first-trimester combined test. Overall, 69.6% of Black pregnancies skipped both tests versus 16.5% in the White group (P<0.001).
CONCLUSIONS
Significant disparities in prenatal care and NIPT adherence were observed among pregnant women of diverse ethnic backgrounds. Lower cf-DNA adhesion and limited adherence to first-trimester screening were observed among any ethnicities. These findings highlight the critical need for targeted interventions and policies to reduce barriers and facilitate access to prenatal care for all women.
PubMed: 38953910
DOI: 10.23736/S2724-606X.24.05530-1 -
Cancer Epidemiology, Biomarkers &... Jul 2024African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been...
BACKGROUND
African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in immune response have been minimal. Therefore, we compared components of the tumor microenvironment among African Americans and non-Hispanic Whites diagnosed with non-small cell lung cancer (NSCLC) based on PD-L1 or tertiary lymphoid structure (TLS) status to identify differences of translational relevance.
METHODS
Using a cohort of 280 NSCLC patients from the INHALE study (non-Hispanic White: n=155; African American: n=125), we evaluated PD-L1 tumor proportion score (<1% vs. ≥1%) and TLS status (presence/absence), comparing differences within the tumor microenvironment based on immune cell distribution and differential expression of genes.
RESULTS
Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than non-Hispanic Whites. In addition, gene expression patterns in African American PD-L1 positive samples suggest these tumors contained greater numbers of γδ T-cells and resting dendritic cells, along with fewer CD8+ T-cells after adjusting for age, sex, pack-years, stage, and histology. Investigation of differential expression of B-cell/plasma cell related genes between the two patient populations revealed that two immunoglobulin genes (IGKV2-29 and IGLL5) were associated with decreased mortality risk in African Americans.
CONCLUSIONS
In the first known race-stratified analysis of tumor microenvironment components in lung cancer based on PD-L1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified that may have therapeutic implications.
IMPACT
Future investigation of racial variation within the tumor microenvironment may help direct the use of immunotherapy.
PubMed: 38953893
DOI: 10.1158/1055-9965.EPI-24-0333 -
Scandinavian Journal of Clinical and... Jul 2024Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the...
INTRODUCTION
Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard.
MATERIAL AND METHOD
MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations.
RESULT
Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (-value = .015), and no significant association was observed with cardiac siderosis (-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (-value = .001), aspartate aminotransferase (AST ((-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload ( value = .36).
CONCLUSION
An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.
PubMed: 38953608
DOI: 10.1080/00365513.2024.2369991 -
General Physiology and Biophysics Jul 2024Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater...
Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; RNA, Circular; Lung Neoplasms; Pilot Projects; Male; Female; Aged; Gene Expression Profiling; Middle Aged; Transcriptome; Gene Expression Regulation, Neoplastic
PubMed: 38953571
DOI: 10.4149/gpb_2024013 -
American Journal of Hematology Jul 2024Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS-MM...
Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS-MM between 2000 and 2022. A matched-control group of MM patients without CNS-MM was used for comparisons. Median age was 63 years. Median time to CNS-MM was 28 months; 6/54 experienced CNS-MM at MM diagnosis. Abnormal lactate dehydrogenase (LDH), high-risk cytogenetics, and extramedullary involvement (EMI), that is, soft tissue plasmacytomas and/or plasma cell leukemia (PCL), were more frequent in CNS-MM versus controls (p < .05); 13/54 had PCL at CNS-MM. The majority had leptomeningeal infiltration (LMI) (66%); 26% had CNS-MM without systemic myeloma; EMI was the strongest predictor for CNS-MM (OR: 6.3). Median overall survival (OS) of CNS-MM patients versus controls was 43 months (95% CI: 32-54) versus 60 months (95% CI: 38-82) (p < .001); treatment of CNS-MM included mainly bortezomib/thalidomide/chemotherapy whereas 20% received novel drugs/immunotherapy combinations; 28 patients underwent cerebrospinal fluid infusions; EMI was the strongest negative predictor for post CNS-MM OS (p = .005; HR: 2.9). Treatment after 2016 predicted significantly for OS (p = .002; HR: 0.27). Median post CNS-MM OS was 4 months (95% CI: 2.6-5.4); in patients treated after 2016 median OS was 12 months. In conclusion, we have demonstrated in this large real-world series that survival of CNS-MM remains poor; however, there is a positive impact of treatment after 2016, related to the efficacy of modern anti-myeloma therapy; EMI significantly increases the probability to develop CNS-MM and the risk of post CNS-MM death, indicating a potential need for CNS prophylaxis for those patients.
PubMed: 38953456
DOI: 10.1002/ajh.27425