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Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review. 原发性骨髓纤维化中存在 JAK2、CALR 和 MPL 三阳性驱动突变:病例报告和文献综述。
IF 2 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-13 DOI: 10.1080/16078454.2024.2402106
Long Zhao, Hao Zhang, Juan Chen, Haizhen Ma, Bei Liu
{"title":"Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review.","authors":"Long Zhao, Hao Zhang, Juan Chen, Haizhen Ma, Bei Liu","doi":"10.1080/16078454.2024.2402106","DOIUrl":"https://doi.org/10.1080/16078454.2024.2402106","url":null,"abstract":"<p><strong>Background: </strong>Primary myelofibrosis (PMF) is the most advanced subtype among the classic Philadelphia chromosomenegative myeloproliferative neoplasms (MPNs). A majority of patients carry one of three mutually-exclusive somatic driver mutations: JAK2 (60-65%), CALR (20-25%), or MPL (5%). Co-occurrence of these mutations is rarely reported. Here we report a case with a triple positive combination of JAK2, CALR and MPL driver mutations.</p><p><strong>Case presentation: </strong>A 69-year-old male was admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (COPD) and was found to have splenomegaly and leukocytosis. Nextgeneration revealed JAK2, CALR, MPL mutations, and additional variants in SF3B1, SRSF2, and STAG2. The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy. Due to nausea, the ruxolitinib dose was reduced. After therapy, spleen volume decreased and hematologic responses were poor. Another genetic mutation of ASXL1 was later found. After adjusting the medication and adding antiemetics, the patient's condition improved.</p><p><strong>Conclusions: </strong>The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hemoglobin J-Auckland: a clinically silent low oxygen affinity variant presenting with persistent asymptomatic hypoxemia at high altitude. 血红蛋白 J-奥克兰:一种临床上无症状的低氧亲和力变异体,在高海拔地区表现为持续性无症状低氧血症。
IF 2 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-23 DOI: 10.1080/16078454.2024.2405751
Ali Alsuheel Asseri, Ibrahim Tawhari, Afaf Haif Qahtani, Ibrahim A Asiri, Husain Alkhaldy
{"title":"Hemoglobin J-Auckland: a clinically silent low oxygen affinity variant presenting with persistent asymptomatic hypoxemia at high altitude.","authors":"Ali Alsuheel Asseri, Ibrahim Tawhari, Afaf Haif Qahtani, Ibrahim A Asiri, Husain Alkhaldy","doi":"10.1080/16078454.2024.2405751","DOIUrl":"https://doi.org/10.1080/16078454.2024.2405751","url":null,"abstract":"<p><strong>Background: </strong>Inherited hemoglobin disorders are common in clinical practice. While qualitative (i.e. sickle cell disease) and quantitative (thalassemia) hemoglobinopathies are usually diagnosed clinically and confirmed through simple laboratory assessments, hemoglobin variants with altered oxygen affinity often go undetected due to their typically silent clinical presentation. Hemoglobin (Hb) J-Auckland, a low oxygen affinity hemoglobin variant first described in 1987 in Auckland, New Zealand, is one such silent disorder.</p><p><strong>Case presentation: </strong>We report for the first time a clinically evident case of previously undiagnosed Hb J-Auckland in an 8-year-old girl who presented with unexplained hypoxemia at high altitude. Her oxygen level was corrected with supplemental oxygen and when assessed at low altitude. A brief discussion of the diagnostic approach and clinical implications is provided.</p><p><strong>Conclusion: </strong>Standard hemoglobin analysis is essential for the evaluation of suspected altered affinity hemoglobinopathy, and genetic testing is often required for definitive diagnosis. Early recognition and diagnosis of these variants can prevent mismanagement and improve patient outcomes.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phase II study of pegaspargase, etoposide, gemcitabine (PEG) followed by involved-field radiation therapy in early-stage extranodal natural killer/T-cell lymphoma. 对早期结节外自然杀伤/T细胞淋巴瘤进行的聚合酶、依托泊苷、吉西他滨(PEG)和介入场放射治疗的II期研究。
IF 2 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-13 DOI: 10.1080/16078454.2024.2402102
Demei Feng, Zhimin Yan, Bibo Fu, Shenrui Bai, Lewei Zhu, Robert Peter Gale, Zhongjun Xia, Yang Liang, Hua Wang
{"title":"Phase II study of pegaspargase, etoposide, gemcitabine (PEG) followed by involved-field radiation therapy in early-stage extranodal natural killer/T-cell lymphoma.","authors":"Demei Feng, Zhimin Yan, Bibo Fu, Shenrui Bai, Lewei Zhu, Robert Peter Gale, Zhongjun Xia, Yang Liang, Hua Wang","doi":"10.1080/16078454.2024.2402102","DOIUrl":"10.1080/16078454.2024.2402102","url":null,"abstract":"<p><strong>Objective: </strong>The prognosis of extra-nodal NK/T cell lymphoma (ENKTL) is poor, and the optimal therapy remains controversial. This study aims to evaluate the safety and efficacy of a new combined modality therapy.</p><p><strong>Methods: </strong>Phase-2 study of pegaspargase, etoposide and gemcitabine (PEG) combined with involved field radiation therapy (IFRT) in newly-diagnosed patients with early-stage ENKTL. Patients received 4 course of PEG followed by IFRT. The primary endpoints were complete response (CR), partial response (PR), and objective response rate (ORR) after IFRT. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and adverse events.</p><p><strong>Results: </strong>34 consecutive patients with Ann Arbor stage I/II were enrolled. 3 patients progressed on PEG, while the remaining 31 received IFRT. The ORR was 88.2% (30/34), included 28 (82.4%) complete and 2 (5.8%) partial responses. With a median follow-up of 56.0 months (Interquartile Range [IQR], 36.0-66.9 months), the estimated 5-year PFS and OS were 87.4% (95% Confidence Interval [CI],69.5%-94.8%) and 97.1% (95%CI, 80.1%-99.6%), respectively. Most adverse events were hematological and easily managed.</p><p><strong>Conclusions: </strong>PEG followed by IFRT is a safe and effective initial therapy for early-stage ENKTL, demonstrating impressive PFS and OS rates. This promising approach warrants further validation in a randomized controlled trial (Registered at Clinicaltrials.gov NCT02705508).<b>Trial registration:</b> ClinicalTrials.gov identifier: NCT02705508.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hub genes and associated drugs for multiple myeloma with 1q21+: identified by bioinformatic analysis. 1q21+ 多发性骨髓瘤的枢纽基因和相关药物:通过生物信息学分析确定。
IF 1.9 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-03-03 DOI: 10.1080/16078454.2024.2323890
Zhiqiang Xu, Jieni Yu, Yamei Chen
{"title":"Hub genes and associated drugs for multiple myeloma with 1q21+: identified by bioinformatic analysis.","authors":"Zhiqiang Xu, Jieni Yu, Yamei Chen","doi":"10.1080/16078454.2024.2323890","DOIUrl":"10.1080/16078454.2024.2323890","url":null,"abstract":"<p><p>While 1q21+ was common genetic alteration and found to have adverse effect on prognosis, the underlying genes remain unclear. Identification of related genes may provide additional help for rational intervention. The microarray dataset GSE2658 associated with MM was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were obtained, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate their functions. The hub genes were derived from the combined results of up-regulated DEGs and weighted gene coexpression network analysis (WGCNA). The receiver operating characteristic (ROC) curves of hub genes were plotted to evaluate correlation with 1q21+. Survival analysis and drug-gene interaction of hub genes were performed separately to find the prognostic value and potential targeted drugs. A total of 55 DEGs were identified. GO and KEGG pathway analyses suggested that the DEGs were related to several pathways of cell proliferation. <i>NVL, IL6R, DUSP23</i> were proven to be highly correlated with 1q21+ and have adverse effects on prognosis. <i>IL6R, DUSP23</i> were matched to known interaction-drug. This study revealed potential roles of hub genes in the pathogenesis and progression of MM with 1q21+, further investigations are needed to elucidate the mechanisms.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pre-treatment [18F]FDG PET/CT for assessing bone marrow involvement and prognosis in patients with newly diagnosed peripheral T-cell lymphoma. 治疗前[18F]FDG PET/CT用于评估新诊断的外周T细胞淋巴瘤患者的骨髓受累情况和预后。
IF 1.9 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-03-11 DOI: 10.1080/16078454.2024.2325317
Jing Chen, Yi Zhao
{"title":"Pre-treatment [<sup>18</sup>F]FDG PET/CT for assessing bone marrow involvement and prognosis in patients with newly diagnosed peripheral T-cell lymphoma.","authors":"Jing Chen, Yi Zhao","doi":"10.1080/16078454.2024.2325317","DOIUrl":"10.1080/16078454.2024.2325317","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the value of [<sup>18</sup>F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in assessing bone marrow involvement (BMI) and prognosis in newly diagnosed peripheral T-cell lymphomas (PTCLs) before treatment.</p><p><strong>Methods: </strong>This retrospective study included 201 eligible PTCLs who received pre-bone marrow biopsy (BMB) and PET/CT. The status of bone marrow (BM) by PET was assessed using a visual examination and a quantitative index (the maximal standardized uptake value [SUV<sub>max</sub>] of BM divided by the SUV<sub>max</sub> of the liver [M/L]).</p><p><strong>Results: </strong>Totally 148 patients had no evidence of BMI by PET or BMB; BMI was detected by both methods in 16 patients. The sensitivity and specificity of PET/CT for patients with confirmed BMI by BMB were 43.2% and 90.2%, respectively (κ =  0.353). In addition, 25 patients assessed by PET/CT staging (having stage I to II disease) had no evidence of BMI detected by both PET/CT and BMB. Image-guided biopsy was also recommended when PET/CT showed a focal FDG uptake outside the iliac crest. Survival analysis revealed that BMB was significant for overall survival (OS) (<i>P</i> = 0.020) while M/L for both progression free survival (<i>P</i> = 0.002) and OS (<i>P</i> < 0.001). In multivariate analysis, M/L (HR 1.825, 95% CI 1.071-3.110, <i>P</i> = 0.027) was an independent prognostic factor for OS. There were no statistical differences at the genetic level about BMI confirmed by PET or BMB.</p><p><strong>Conclusion: </strong>PET/CT has a complementary role in assessing BMI and an ability to predict prognosis in PTCL patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current status of conditioning regimens in haploidentical hematopoietic cell transplantation. 单倍体造血细胞移植的调理方案现状。
IF 1.9 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-03-21 DOI: 10.1080/16078454.2024.2332866
Junichi Sugita, Masamitsu Yanada
{"title":"Current status of conditioning regimens in haploidentical hematopoietic cell transplantation.","authors":"Junichi Sugita, Masamitsu Yanada","doi":"10.1080/16078454.2024.2332866","DOIUrl":"10.1080/16078454.2024.2332866","url":null,"abstract":"<p><p>The development of effective prophylaxis strategies against graft-versus-host disease (GVHD) has contributed to the widespread use of haploidentical related hematopoietic cell transplantation (Haplo-HCT). Currently, GVHD prophylaxis containing posttransplant cyclophosphamide (PTCY) is considered the standard of care in Haplo-HCT, and recent studies have shown comparable results for PTCY-based Haplo-HCT and HCT from other donor sources. The conditioning regimen plays an important role in eradicating tumor cells to prevent disease relapse and suppressing the recipient's immune system to facilitate engraftment. PTCY-based Haplo-HCT was initially developed using a nonmyeloablative conditioning regimen consisting of fludarabine, cyclophosphamide and low-dose total body irradiation, but high relapse rates reinforced the need to intensify the conditioning regimen. In this respect, various myeloablative and reduced-intensity conditioning regimens have been investigated. However, the optimal conditioning regimens for PTCY-based Haplo-HCT have not yet been established, and this issue needs to be addressed based on data from patients undergoing the procedure. In this article, we review the existing literature on conditioning regimens for PTCY-based Haplo-HCT and discuss future perspectives.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The influence of dead space in blood sampling needle on FVIII level and pharmacokinetic profiles in children with hemophilia. 采血针中的死腔对血友病患儿 FVIII 水平和药代动力学特征的影响。
IF 1.9 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-02-12 DOI: 10.1080/16078454.2024.2314871
Yingzi Zhen, Di Ai, Kun Huang, Gang Li, Zhenping Chen, Runhui Wu
{"title":"The influence of dead space in blood sampling needle on FVIII level and pharmacokinetic profiles in children with hemophilia.","authors":"Yingzi Zhen, Di Ai, Kun Huang, Gang Li, Zhenping Chen, Runhui Wu","doi":"10.1080/16078454.2024.2314871","DOIUrl":"10.1080/16078454.2024.2314871","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia.</p><p><strong>Methods: </strong>Children (<18 years) with severe hemophilia A were enrolled. After three days' washout-period, blood samples were collected at pre-dose, 1 h, 3 h, 9 h, 24 h and 48 h post-infusion. At each timepoint, two 2 mL vacuum tubes with 3.2% trisodium citrate were used. The first tube was signed as 'non-standard' (NS) and the second tube was signed as 'standard' (S). FVIII activities were evaluated by one-stage assay. WAPPS-Hemo was used to generate PK profiles like half-life time (t<sub>1/2</sub>), clearance (CL), trough level and time to 1, 2 and 5IU/dL after a dose of 50 ± 10IU/dL. The FVIII activities at 9 h and 24 h post-infusion were put into WAPPS and thus brought four combinations by true or biased FVIII level that used.</p><p><strong>Result: </strong>Compared with standard-collected blood samples, prolonged APTT results (<i>P</i>-values < 0.01) and decreased FVIII activity (<i>P</i>-values < 0.05) were revealed in those non-standard blood samples. The corresponding bias was in positive relation to both APTT-S (r = 0.44, <i>P </i>< 0.0001) and FVIII-S level(r = 0.68, <i>P </i>< 0.001). The FVIII bias percentage got larger as FVIII-S level reduced (r = -0.24, <i>P </i>< 0.01). During the four combinations of FVIII activity at 9 h and 24 h, statistically longer t<sub>1/2</sub>, lower CL and longer time to 1, 2 or 5IU/dL were observed in 9H-S&24H-S group and 9H-NS&24H-S group.</p><p><strong>Conclusion: </strong>While using vacuum tubes for clotting indicators and PK profiles, the dead space of blood sampling needle should be eliminated in advance.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular vesicle-mediated regulation of imatinib resistance in chronic myeloid leukemia via the miR-629-5p/SENP2/PI3K/AKT/mTOR axis. 细胞外囊泡通过 miR-629-5p/SENP2/PI3K/AKT/mTOR 轴介导对慢性髓性白血病中伊马替尼耐药性的调控
IF 2 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-07-26 DOI: 10.1080/16078454.2024.2379597
Yaqin Jiang, Shishan Xiao, Shengwen Huang, Xuemei Zhao, Siruiyun Ding, Qianqian Huang, Wei Xiao, Zhe Li, Hongqian Zhu
{"title":"Extracellular vesicle-mediated regulation of imatinib resistance in chronic myeloid leukemia via the miR-629-5p/SENP2/PI3K/AKT/mTOR axis.","authors":"Yaqin Jiang, Shishan Xiao, Shengwen Huang, Xuemei Zhao, Siruiyun Ding, Qianqian Huang, Wei Xiao, Zhe Li, Hongqian Zhu","doi":"10.1080/16078454.2024.2379597","DOIUrl":"10.1080/16078454.2024.2379597","url":null,"abstract":"<p><strong>Background: </strong>Imatinib (IM) is the primary treatment for patients with chronic-phase CML (CML-CP). However, an increasing number of CML-CP patients have developed resistance to IM. Our study aims to explore the expression of miR-629-5p in extracellular vesicles (EVs) from both IM-sensitive (K562) and resistant (K562-Re) CML cell lines and to investigate the impact of regulating miR-629-5p expression on the biological characteristics of K562 and K562-Re cells.</p><p><strong>Methods: </strong>Assess miR-629-5p expression levels in IM-sensitive and resistant CML cell lines. Separate EVs and verify it. EVs from K562-Re cells were co-cultured with K562 cells to detect the expression level of miR-629-5p. Target genes of miR-629-5p were determined and validated through luciferase experiments. Examined by manipulating miR-629-5p expression in cells using transfection techniques. The expression level of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway after IM was detected in CML cell lines. In K562-Re cells, the expression level of phosphorylated protein in the PI3K/AKT/mTOR signaling pathway was detected after single transfection of miR-629-5p inhibitor and cotransfection of miR-629-5p inhibitor and siSENP2.</p><p><strong>Results: </strong>Increasing concentrations of EVs from K562-Re cells elevated miR-629-5p expression levels. The expression levels of miR-629-5p in CML cells varied with IM concentration and influenced the biological characteristics of cells. SENP2 was identified as a target gene of miR-629-5p. Furthermore, miR-629-5p was found to modulate the SENP2/PI3K/AKT/mTOR pathway, impacting IM resistance in CML cells.</p><p><strong>Conclusion: </strong>EVs from IM-resistant CML cells alter the expression of miR-629-5p in sensitive cells, activating the SENP2/PI3K/AKT/mTOR pathway and leading to IM resistance.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Function of NLRP3 inflammasome activation in multiple myeloma. 多发性骨髓瘤中 NLRP3 炎症小体激活的功能。
IF 2 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-13 DOI: 10.1080/16078454.2024.2399367
Xiaorong Zhu, Jie Yu, Mingqiang Hua, Ning Xu, Lianjuan Wang, Lingkai Chen, Yanhong Jia, Xueyun Zhao
{"title":"Function of NLRP3 inflammasome activation in multiple myeloma.","authors":"Xiaorong Zhu, Jie Yu, Mingqiang Hua, Ning Xu, Lianjuan Wang, Lingkai Chen, Yanhong Jia, Xueyun Zhao","doi":"10.1080/16078454.2024.2399367","DOIUrl":"https://doi.org/10.1080/16078454.2024.2399367","url":null,"abstract":"<p><strong>Objective: </strong>The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.</p><p><strong>Methods: </strong>First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.</p><p><strong>Result: </strong>1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (<i>P </i>< 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (<i>P </i>= 0.03, <i>P </i>= 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (<i>P </i>< 0.05). The expressions of caspase-1 mRNA(<i>P </i>= 0.016) and IL-1β mRNA(<i>P </i>= 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (<i>P </i>= 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (<i>P </i>= 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (<i>P </i>= 0.03).</p><p><strong>Conclusion: </strong>1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis. 达拉单抗对肾功能不全的多发性骨髓瘤患者的疗效:系统综述和荟萃分析。
IF 2 4区 医学
Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-09 DOI: 10.1080/16078454.2024.2399430
Hua Jiang, Lu Li, Meiyu Guo, Meizhang Li, Hao Wu, Xiaomei Chen, Mingzhao Gao, Qianqian Xu, Jia Mi, Canchan Cui, Weijun Fu
{"title":"Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.","authors":"Hua Jiang, Lu Li, Meiyu Guo, Meizhang Li, Hao Wu, Xiaomei Chen, Mingzhao Gao, Qianqian Xu, Jia Mi, Canchan Cui, Weijun Fu","doi":"10.1080/16078454.2024.2399430","DOIUrl":"10.1080/16078454.2024.2399430","url":null,"abstract":"<p><strong>Background: </strong>Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI.</p><p><strong>Methods: </strong>We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time.</p><p><strong>Conclusions: </strong>Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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