Hemato最新文献 - Book学术

The Novel Anti-Cancer Agent, SpiD3, Is Cytotoxic in CLL Cells Resistant to Ibrutinib or Venetoclax. 新型抗癌剂 SpiD3 对伊布替尼或 Venetoclax 耐药的 CLL 细胞具有细胞毒性。

IF 0.9

Hemato Pub Date : 2024-09-01 Epub Date: 2024-08-27 DOI: 10.3390/hemato5030024

Alexandria P Eiken, Elizabeth Schmitz, Erin M Drengler, Audrey L Smith, Sydney A Skupa, Kabhilan Mohan, Sandeep Rana, Sarbjit Singh, Jayapal Reddy Mallareddy, Grinu Mathew, Amarnath Natarajan, Dalia El-Gamal

{"title":"The Novel Anti-Cancer Agent, SpiD3, Is Cytotoxic in CLL Cells Resistant to Ibrutinib or Venetoclax.","authors":"Alexandria P Eiken, Elizabeth Schmitz, Erin M Drengler, Audrey L Smith, Sydney A Skupa, Kabhilan Mohan, Sandeep Rana, Sarbjit Singh, Jayapal Reddy Mallareddy, Grinu Mathew, Amarnath Natarajan, Dalia El-Gamal","doi":"10.3390/hemato5030024","DOIUrl":"https://doi.org/10.3390/hemato5030024","url":null,"abstract":"Background: B-cell receptor (BCR) signaling is a central driver in chronic lymphocytic leukemia (CLL), along with the activation of pro-survival pathways (e.g., NF-κB) and aberrant anti-apoptotic mechanisms (e.g., BCL2) culminating to CLL cell survival and drug resistance. Front-line targeted therapies such as ibrutinib (BTK inhibitor) and venetoclax (BCL2 inhibitor) have radically improved CLL management. Yet, persisting CLL cells lead to relapse in ~20% of patients, signifying the unmet need of inhibitor-resistant refractory CLL. SpiD3 is a novel spirocyclic dimer of analog 19 that displays NF-κB inhibitory activity and preclinical anti-cancer properties. Recently, we have shown that SpiD3 inhibits CLL cell proliferation and induces cytotoxicity by promoting futile activation of the unfolded protein response (UPR) pathway and generation of reactive oxygen species (ROS), resulting in the inhibition of protein synthesis in CLL cells.Methods: We performed RNA-sequencing using CLL cells rendered resistant to ibrutinib and venetoclax to explore potential vulnerabilities in inhibitor-resistant and SpiD3-treated CLL cells.Results: The transcriptomic analysis of ibrutinib- or venetoclax-resistant CLL cell lines revealed ferroptosis, UPR signaling, and oxidative stress to be among the top pathways modulated by SpiD3 treatment. By examining SpiD3-induced protein aggregation, ROS production, and ferroptosis in inhibitor-resistant CLL cells, our findings demonstrate cytotoxicity following SpiD3 treatment in cell lines resistant to current front-line CLL therapeutics.Conclusions: Our results substantiate the development of SpiD3 as a novel therapeutic agent for relapsed/refractory CLL disease.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":"5 3","pages":"321-339"},"PeriodicalIF":0.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthetic Lethality Approaches in Acute Lymphoblastic Leukemia 急性淋巴细胞白血病的合成致死方法

Hemato Pub Date : 2023-12-26 DOI: 10.3390/hemato5010002

F. A. Lagunas-Rangel, V. Chávez-Valencia

引用次数: 0

Hemato Keeps You Updated on the Research in Hematology Hemato 为您提供血液学研究的最新信息

Hemato Pub Date : 2023-12-25 DOI: 10.3390/hemato5010001

Antonino Carbone

引用次数: 0

The Role of Platelet Molecules in Risk Stratification of Patients with COVID-19 血小板分子在 COVID-19 患者风险分层中的作用

Hemato Pub Date : 2023-11-30 DOI: 10.3390/hemato4040029

Lívia de Oliveira Sales, L. L. B. de Oliveira, Jean Breno Silveira da Silva, M. O. de Moraes Filho, M. E. D. de Moraes, R. Montenegro, C. Moreira-Nunes

{"title":"The Role of Platelet Molecules in Risk Stratification of Patients with COVID-19","authors":"Lívia de Oliveira Sales, L. L. B. de Oliveira, Jean Breno Silveira da Silva, M. O. de Moraes Filho, M. E. D. de Moraes, R. Montenegro, C. Moreira-Nunes","doi":"10.3390/hemato4040029","DOIUrl":"https://doi.org/10.3390/hemato4040029","url":null,"abstract":"The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China and is responsible for Coronavirus disease (COVID-19). Despite being well tolerated by most patients, a fraction of cases evolve into a potentially fatal condition requiring intensive care. In addition to respiratory complications, several studies have reported cases of patients who developed intense thrombosis, including acute myocardial infarction and ischemic stroke, as well as the presence of elevated coagulation markers. Evidence has shown that the virus can interact directly with platelets and modulate their thrombotic and inflammatory functions, with significant prognostic implications. It is important to highlight that the emerging literature shows that when hyperactive these cells can act as pro-viral infections both in transporting their particles and in increasing inflammation, leading to a hyperinflammatory state and consequent clinical worsening. In this review, we searched for studies available in public databases and discussed the interaction of platelet biomarkers in the pathogenesis of COVID-19. In this context, understanding the mechanism of SARS-CoV-2 and these cells in different clinical conditions could help us to understand the coagulation and inflammation profiles of critically ill patients with the disease, guiding faster clinical management and enabling the reuse and targeting of more efficient therapies.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":"190 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139206412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibril-Forming Organelles in Mesangial Cells in Renal Biopsies from Patients with Light-Chain-Associated Amyloidosis 轻链相关淀粉样变性患者肾活检组织间质细胞中的纤维状细胞器

Hemato Pub Date : 2023-11-23 DOI: 10.3390/hemato4040028

Guillermo A. Herrera, J. Teng, Chun Zeng, L. Del Pozo-Yauner, Bing Liu, E. Turbat-Herrera

{"title":"Fibril-Forming Organelles in Mesangial Cells in Renal Biopsies from Patients with Light-Chain-Associated Amyloidosis","authors":"Guillermo A. Herrera, J. Teng, Chun Zeng, L. Del Pozo-Yauner, Bing Liu, E. Turbat-Herrera","doi":"10.3390/hemato4040028","DOIUrl":"https://doi.org/10.3390/hemato4040028","url":null,"abstract":"The process of light-chain-associated amyloid (AL-Am) fibril formation in unique organelles (fibril-forming organelles) with lysosomal features has been documented in vitro in renal mesangial cells incubated with amyloidogenic light chains using electron microscopy and lysosomal gradient centrifugation to visualize intricate interactions between monoclonal light chains and endosomes/lysosomes. It is important to determine whether this process also occurs in vivo in the human renal mesangium. The present study analyzes 13 renal biopsies from patients with renal AL-amyloidosis and utilizes ultrastructural labeling techniques to define the nature and function of these organelles. Organelles were labeled for lysosomal-associated membrane protein (LAMP) and CD-68 (a macrophage marker). Furthermore, lambda was also localized inside these structures in transformed mesangial cells with a macrophage phenotype. These 11 cases from renal biopsies with a diagnosis of AL-amyloidosis (5 kappa and 8 lambda light-chain-associated) were examined ultrastructurally. All of the cases exhibited numerous fibrils forming organelles in approximately 40–50% of the remaining mesangial cells. All of the cases revealed mesangial cells engaged in active amyloidogenesis. Fibril-forming organelles are organelles with morphological/immunohistochemical and biochemical characteristics of lysosomes but with a unique, peculiar morphology. Five cases of other glomerular disorders used as controls were also carefully scrutinized for fibril-forming organelles and failed to show any. In the AL-amyloid renal cases, there was an intricate interaction between the fibril-forming organelles and lambda-/kappa-containing amyloid fibrils, supporting the notion that the monoclonal light chains participated in their formation.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":"53 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139245623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance 意义不明的单克隆γ病的地理流行模式和可改变的危险因素

Hemato Pub Date : 2023-11-01 DOI: 10.3390/hemato4040027

Karina P. Verma, Rebecca Steuer, Camille V. Edwards

{"title":"Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance","authors":"Karina P. Verma, Rebecca Steuer, Camille V. Edwards","doi":"10.3390/hemato4040027","DOIUrl":"https://doi.org/10.3390/hemato4040027","url":null,"abstract":"Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant plasma cell disorder with an etiology that is incompletely understood. Modifiable risk factors and genetic predispositions likely interact to increase MGUS risk in specific individuals and populations. Identifying geographic prevalence patterns and modifiable risk factors is critical for understanding the etiology of MGUS. The aim of this review was to outline original research on MGUS prevalence across geographic locations and modifiable risk factors. We conducted a systematic review of 39 eligible studies from PubMed®, Embase®, and Web of Science® written in English and published by February 2023. Our protocol was registered in accordance with PROSPERO guidelines. Studies were synthesized using Research Electronic Data Capture and appraised using the National Heart, Lung, and Blood Institute study quality assessment tools. The prevalence of MGUS ranged from 0.24% to 9% across geographic locations. Modifiable risk factors for MGUS include infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors, environmental exposures, and ionizing radiation. Therefore, the development of MGUS may be related to chronic antigenic stimulation and genetic aberrations that promote clonal proliferation of plasma cells. Prospective studies assessing gene–environment interactions are needed to further define risk factors for MGUS and inform screening and preventative strategies.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":"60 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135221535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of PET in the Diagnosis and Disease Activity Assessment in Large Vessel Vasculitis PET在大血管炎诊断和疾病活动性评估中的作用

Hemato Pub Date : 2023-10-30 DOI: 10.3390/hemato4040026

Chiara Marvisi, Elena Galli, Caterina Ricordi, Rexhep Durmo, Massimo Roncali, Francesco Muratore, Carlo Salvarani, Annibale Versari

引用次数: 0

Methotrexate-Induced Subacute Combined Degeneration in Acute Lymphoblastic Leukemia with CNS Relapse May Be Reversible 甲氨蝶呤诱导的伴有中枢神经系统复发的急性淋巴细胞白血病亚急性合并变性可能是可逆的

Hemato Pub Date : 2023-10-16 DOI: 10.3390/hemato4040025

David Bared Dukenik, Deborah Soong, Wenhui Li, Ellen Madarang, Justin Watts, Justin Taylor

引用次数: 0

Coagulation Profiles in Humans Exposed to Exertional Hypobaric Decompression Stress Determined by Calibrated Automated Thrombogram 通过校准的自动血栓图确定暴露于劳力低压减压压力下的人的凝血特征

Hemato Pub Date : 2023-10-01 DOI: 10.3390/hemato4040024

Leigh A. Madden, Rebecca V. Vince, Victoria C. Edwards, Vivienne M. Lee, Desmond M. Connolly

{"title":"Coagulation Profiles in Humans Exposed to Exertional Hypobaric Decompression Stress Determined by Calibrated Automated Thrombogram","authors":"Leigh A. Madden, Rebecca V. Vince, Victoria C. Edwards, Vivienne M. Lee, Desmond M. Connolly","doi":"10.3390/hemato4040024","DOIUrl":"https://doi.org/10.3390/hemato4040024","url":null,"abstract":"The blood coagulation response to decompression stress in humans has yet to be fully investigated. Here we utilised calibrated automated thrombogram (CAT) on samples from healthy volunteers exposed to decompression stress to investigate real-time thrombin generation. To induce decompression stress, fifteen apparently healthy males (age 20–50 yr) were exposed to two consecutive ascents to 25,000 ft for 60 min (1st ascent) and then 90 min (2nd ascent) while breathing 100% oxygen. Citrated blood samples were taken prior to exposure (T0), following the 2nd ascent (T8) and at 24 h (T24). Thrombin generation curves were obtained using ThrombinoscopeTM. Parameters determined were lag time (LAG), time to peak (TTP), peak thrombin (PEAK), endogenous thrombin potential (ETP) and velocity index (VEL). Of the 15 subjects, 12 had validated coagulation profiles. TTP and ETP showed no significant differences. However, there was a significant increase in VEL from T0 to T8 (p = 0.025) and from T8 to T24 (p = 0.043). A non-significant trend of an overall increase in PEAK was also observed from T0 to T8 (p = 0.069) and from T8 to T24 (p = 0.098). PEAK and VEL were found to be correlated. Taken together, these two parameters suggest an overall shift towards a more procoagulant profile following hypobaric stress.","PeriodicalId":93705,"journal":{"name":"Hemato","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135459353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Imaging of Vascular Graft/Endograft Infection with Radiolabeled White Blood Cell Scan and [18F]FDG PET/CT 血管移植/内移植感染的放射标记白细胞扫描和FDG PET/CT成像[18F]

Hemato Pub Date : 2023-09-22 DOI: 10.3390/hemato4040023

Ringo Manta, Chiara Lauri, Maurizio Taurino, Alberto Signore

引用次数: 0