Pub Date : 2024-12-01Epub Date: 2024-06-18DOI: 10.1080/16078454.2024.2366718
Pongthep Vittayawacharin, Piyanuch Kongtim, Stefan O Ciurea
Outcomes of haploidentical hematopoietic stem cell transplantation (haplo-SCT) have improved over time. Graft failure and graft-versus-host disease (GVHD), which were important complications in major human leukocyte antigen (HLA)-disparity stem cell transplantation, have significantly decreased. These improvements have led to an exponential increase in the use of haploidentical donors for transplantation, as well as in the number of publications evaluating haplo-SCT outcomes. Many studies focused on factors important in donor selection, novel conditioning regimens or GVHD prophylaxis, the impact of donor-specific anti-HLA antibodies (DSA), as well as strategies to prevent disease relapse post-transplant. DSA represents an important limitation and multimodality desensitization protocols, including plasma exchange, rituximab, intravenous immunoglobulin and donor buffy coat infusion, can contribute to the successful engraftment in patients with high DSA levels and is currently the standard therapy for highly allosensitized individuals. With regards to donor selection, younger donors are preferred due to lower risk of complications and better transplant outcomes. Moreover, recent studies also showed that younger haploidentical donors may be a better choice than older-matched unrelated donors. Improvement of disease relapse remains a top priority, and several studies have demonstrated that higher natural killer (NK) cell numbers early post-transplant are associated with improved outcomes. Prospective studies have started to assess the role of NK cell administration in decreasing post-transplant relapse. These studies suggest that the incorporation of other cell products post-transplant, including the administration of chimeric antigen receptor T-cells, should be explored in the future.
随着时间的推移,单倍体造血干细胞移植(haplo-SCT)的结果有所改善。移植物失败和移植物抗宿主疾病(GVHD)是主要人类白细胞抗原(HLA)差异干细胞移植的重要并发症,但现在已显著减少。这些改善导致使用单倍体供体进行移植的人数呈指数增长,评估单倍体干细胞移植结果的出版物数量也呈指数增长。许多研究关注供体选择的重要因素、新型调理方案或 GVHD 预防、供体特异性抗 HLA 抗体 (DSA) 的影响以及预防移植后疾病复发的策略。DSA是一个重要的限制因素,多模式脱敏方案,包括血浆置换、利妥昔单抗、静脉注射免疫球蛋白和输注供体水溶液,有助于高DSA水平患者的成功移植,是目前治疗高度异体敏感患者的标准疗法。在供体选择方面,年轻供体是首选,因为并发症风险较低,移植效果较好。此外,最近的研究还表明,与年龄较大的非血缘配型供体相比,年轻的单倍体供体可能是更好的选择。改善疾病复发仍是当务之急,多项研究表明,移植后早期较高的自然杀伤(NK)细胞数量与改善预后有关。前瞻性研究已开始评估 NK 细胞用药在减少移植后复发方面的作用。这些研究表明,未来应探索在移植后使用其他细胞产品,包括使用嵌合抗原受体 T 细胞。
{"title":"Future directions in haploidentical hematopoietic stem cell transplantation.","authors":"Pongthep Vittayawacharin, Piyanuch Kongtim, Stefan O Ciurea","doi":"10.1080/16078454.2024.2366718","DOIUrl":"10.1080/16078454.2024.2366718","url":null,"abstract":"<p><p>Outcomes of haploidentical hematopoietic stem cell transplantation (haplo-SCT) have improved over time. Graft failure and graft-versus-host disease (GVHD), which were important complications in major human leukocyte antigen (HLA)-disparity stem cell transplantation, have significantly decreased. These improvements have led to an exponential increase in the use of haploidentical donors for transplantation, as well as in the number of publications evaluating haplo-SCT outcomes. Many studies focused on factors important in donor selection, novel conditioning regimens or GVHD prophylaxis, the impact of donor-specific anti-HLA antibodies (DSA), as well as strategies to prevent disease relapse post-transplant. DSA represents an important limitation and multimodality desensitization protocols, including plasma exchange, rituximab, intravenous immunoglobulin and donor buffy coat infusion, can contribute to the successful engraftment in patients with high DSA levels and is currently the standard therapy for highly allosensitized individuals. With regards to donor selection, younger donors are preferred due to lower risk of complications and better transplant outcomes. Moreover, recent studies also showed that younger haploidentical donors may be a better choice than older-matched unrelated donors. Improvement of disease relapse remains a top priority, and several studies have demonstrated that higher natural killer (NK) cell numbers early post-transplant are associated with improved outcomes. Prospective studies have started to assess the role of NK cell administration in decreasing post-transplant relapse. These studies suggest that the incorporation of other cell products post-transplant, including the administration of chimeric antigen receptor T-cells, should be explored in the future.</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":"141418703","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}
Pub Date : 2024-12-01Epub Date: 2024-07-12DOI: 10.1080/16078454.2024.2372482
Xiuli Wang, Qiyuan Zhou, Wen Yang, Hui Bi, Honghui Wang, Yacan Wang, Yadong Du, Lin Liu, Yuebo Liu, Liefen Yin, Jin Yao, Jingxing Yu, Wei Tao, Yongchun Zhou, Zeping Zhou
Background: CD83 are closely related to the pathogenesis of immune thrombocytopenia (ITP), but the exact mechanism remains unclear.
Aim: To explore the relationship between CD83 and CD4+ T cell subsets and clarify the role of CD83 in the pathogenesis of ITP.
Methods: RT-qPCR and Flow cytometry were used to illustrate CD83 expression. The downregulation and overexpression of DC-CD83 were co-cultured with CD4+ T cells to detect cell proliferation, co-cultured supernatant cytokines and Tregs expression.
Results: The results indicate that the ITP patients showed higher expression of CD83 than the healthy controls. The proliferation of CD4+ T cells was inhibited by downregulation of DCs-CD83 but promoted by overexpression of DCs-CD83. siRNA-CD83 inhibited proinflammatory IFN-γ and IL-17 secretion while raising TGF-β, IL-10 concentrations. Overexpression of DCs-CD83 promoted Tregs expression.
Conclusion: The Th1/Th2 and Th17/Tregs polarization were reversed via interfering DCs with siRNA-CD83. CD83 plays an important role in ITP pathogenesis, suggesting novel treatment for ITP patients.
{"title":"The role of CD83 in the pathogenesis of immune thrombocytopenia.","authors":"Xiuli Wang, Qiyuan Zhou, Wen Yang, Hui Bi, Honghui Wang, Yacan Wang, Yadong Du, Lin Liu, Yuebo Liu, Liefen Yin, Jin Yao, Jingxing Yu, Wei Tao, Yongchun Zhou, Zeping Zhou","doi":"10.1080/16078454.2024.2372482","DOIUrl":"https://doi.org/10.1080/16078454.2024.2372482","url":null,"abstract":"<p><strong>Background: </strong>CD83 are closely related to the pathogenesis of immune thrombocytopenia (ITP), but the exact mechanism remains unclear.</p><p><strong>Aim: </strong>To explore the relationship between CD83 and CD4<sup>+</sup> T cell subsets and clarify the role of CD83 in the pathogenesis of ITP.</p><p><strong>Methods: </strong>RT-qPCR and Flow cytometry were used to illustrate CD83 expression. The downregulation and overexpression of DC-CD83 were co-cultured with CD4<sup>+</sup> T cells to detect cell proliferation, co-cultured supernatant cytokines and Tregs expression.</p><p><strong>Results: </strong>The results indicate that the ITP patients showed higher expression of CD83 than the healthy controls. The proliferation of CD4<sup>+</sup> T cells was inhibited by downregulation of DCs-CD83 but promoted by overexpression of DCs-CD83. siRNA-CD83 inhibited proinflammatory IFN-γ and IL-17 secretion while raising TGF-β, IL-10 concentrations. Overexpression of DCs-CD83 promoted Tregs expression.</p><p><strong>Conclusion: </strong>The Th1/Th2 and Th17/Tregs polarization were reversed via interfering DCs with siRNA-CD83. CD83 plays an important role in ITP pathogenesis, suggesting novel treatment for ITP patients.</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":"141590197","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}
Pub Date : 2024-12-01Epub Date: 2024-05-16DOI: 10.1080/16078454.2024.2338300
Christopher Graham, Mark Litzow
Introduction: The likelihood of finding HLA-matched unrelated donors for rare HLA types and non-white European ancestry continues to be a challenge with less than a 70% chance of finding a full match. Mismatched transplants continue to have high rates of transplant-related mortality. With the near-universal ability to find a haploidentical donor in families, haploidentical transplants have become of more critical importance in ethnic minority groups and patients with rare HLA types.
Methods: Data was collected through clinical trials, review articles, and case reports published in the National Library of Medicine.
Results: The use of improved lymphodepleting conditioning regimens, graft versus host disease (GVHD) prophylaxis using regimens such as post-transplant cyclophosphamide, mycophenolate, and tacrolimus have improved engraftment to nearly 100 percent and reduced transplant-related mortality to less than 20 percent. Attention to donor-specific antibodies (DSAs) with interventions using bortezomib, rituximab, and plasmapheresis has decreased graft failure rates.
Conclusion: With improved prevention of GVHD with interventions such as post-transplant cyclophosphamide and management of DSAs, haploidentical transplants continue to improve transplant-related mortality (TRM) compared to patients who received matched-related donor transplants. While TRM continues to improve, ongoing research with haploidentical transplants will focus on improving graft and donor immunosuppression and identifying the best regimens to improve TRM without compromising relapse-free survival.
{"title":"The use of haploidentical stem cell transplant as an alternative donor source in patients with decreased access to matched unrelated donors.","authors":"Christopher Graham, Mark Litzow","doi":"10.1080/16078454.2024.2338300","DOIUrl":"10.1080/16078454.2024.2338300","url":null,"abstract":"<p><strong>Introduction: </strong>The likelihood of finding HLA-matched unrelated donors for rare HLA types and non-white European ancestry continues to be a challenge with less than a 70% chance of finding a full match. Mismatched transplants continue to have high rates of transplant-related mortality. With the near-universal ability to find a haploidentical donor in families, haploidentical transplants have become of more critical importance in ethnic minority groups and patients with rare HLA types.</p><p><strong>Methods: </strong>Data was collected through clinical trials, review articles, and case reports published in the National Library of Medicine.</p><p><strong>Results: </strong>The use of improved lymphodepleting conditioning regimens, graft versus host disease (GVHD) prophylaxis using regimens such as post-transplant cyclophosphamide, mycophenolate, and tacrolimus have improved engraftment to nearly 100 percent and reduced transplant-related mortality to less than 20 percent. Attention to donor-specific antibodies (DSAs) with interventions using bortezomib, rituximab, and plasmapheresis has decreased graft failure rates.</p><p><strong>Conclusion: </strong>With improved prevention of GVHD with interventions such as post-transplant cyclophosphamide and management of DSAs, haploidentical transplants continue to improve transplant-related mortality (TRM) compared to patients who received matched-related donor transplants. While TRM continues to improve, ongoing research with haploidentical transplants will focus on improving graft and donor immunosuppression and identifying the best regimens to improve TRM without compromising relapse-free survival.</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":"140957043","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}
Pub Date : 2024-12-01Epub Date: 2024-04-30DOI: 10.1080/16078454.2024.2346965
ZhongLi Hu, YanLi Yang, JiaJia Li, ZhongTing Hu
Background: This study aims to investigate the correlation between NK and NKT cell proportion disparities and prognosis in patients with acute myeloid leukemia (AML).
Methods: Forty-four cases of acute myeloid leukemia patients were selected, and flow cytometry was utilized to evaluate the expression of bone marrow NK and NKT cells. Next-generation sequencing technology was employed to detect genetic mutations in these 44 AML patients, and the rates of first induction remission and overall survival were recorded. Comparisons were made to analyze the respective differences in NK and NKT cell proportions among AML patients with various genetic mutations and risk stratifications.
Results: The FLT-3-ITD+ group exhibited a significant increase in the proportion of NK cells compared to the normal control group and FLT3-ITD+/NPM1+ group, whereas the proportion of NKT cells was significantly decreased. Additionally, the CEBPA+ group showed an increased proportion of NKT cells compared to the TP53+ group and ASXL1+ group. The high-risk group had a higher proportion of NK cells than the intermediate-risk group, while the proportion of NKT cells was lower in the high-risk group compared to the intermediate-risk group.Patients achieving first induction remission displayed a higher proportion of NKT cells at initial diagnosis compared to those who did not achieve remission. The distribution of NK cells show significant differences among AML patients in different survival periods.
Conclusion: This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.
{"title":"Genetic mutations and immune microenvironment: unveiling the connection to AML prognosis.","authors":"ZhongLi Hu, YanLi Yang, JiaJia Li, ZhongTing Hu","doi":"10.1080/16078454.2024.2346965","DOIUrl":"https://doi.org/10.1080/16078454.2024.2346965","url":null,"abstract":"<p><strong>Background: </strong>This study aims to investigate the correlation between NK and NKT cell proportion disparities and prognosis in patients with acute myeloid leukemia (AML).</p><p><strong>Methods: </strong>Forty-four cases of acute myeloid leukemia patients were selected, and flow cytometry was utilized to evaluate the expression of bone marrow NK and NKT cells. Next-generation sequencing technology was employed to detect genetic mutations in these 44 AML patients, and the rates of first induction remission and overall survival were recorded. Comparisons were made to analyze the respective differences in NK and NKT cell proportions among AML patients with various genetic mutations and risk stratifications.</p><p><strong>Results: </strong>The FLT-3-ITD+ group exhibited a significant increase in the proportion of NK cells compared to the normal control group and FLT3-ITD+/NPM1+ group, whereas the proportion of NKT cells was significantly decreased. Additionally, the CEBPA+ group showed an increased proportion of NKT cells compared to the TP53+ group and ASXL1+ group. The high-risk group had a higher proportion of NK cells than the intermediate-risk group, while the proportion of NKT cells was lower in the high-risk group compared to the intermediate-risk group.Patients achieving first induction remission displayed a higher proportion of NKT cells at initial diagnosis compared to those who did not achieve remission. The distribution of NK cells show significant differences among AML patients in different survival periods.</p><p><strong>Conclusion: </strong>This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.</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":"140868044","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}
Background: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL.
Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24.
Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL.
Conclusion: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.
{"title":"The prognostic significance of POD24 in peripheral T-cell lymphoma.","authors":"Huimin Chen, Ruixue Ma, Qianqian Zhang, Fengyi Lu, Yuhan Ma, Jingxin Zhou, Jiang Cao, Kunming Qi, Zhiling Yan, Wei Sang, Feng Zhu, Haiying Sun, Depeng Li, Zhenyu Li, Hai Cheng, Kailin Xu, Wei Chen","doi":"10.1080/16078454.2024.2304483","DOIUrl":"10.1080/16078454.2024.2304483","url":null,"abstract":"<p><strong>Background: </strong>Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24.</p><p><strong>Results: </strong>Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; <i>P </i>< 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL.</p><p><strong>Conclusion: </strong>POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.</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":"139512311","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}
Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.
急性髓性白血病(AML)是造血系统相关疾病中常见的血癌,预后较差。研究表明,长非编码 RNA(lncRNA)与包括 AML 在内的多种疾病的发病机制密切相关。然而,具体的分子机制仍不清楚。因此,本研究旨在探讨lncRNA X非活性特异性转录本(lncRNA XIST)对AML的影响及其机制。为了实现我们的目标,我们进行了一些测试。研究利用实时定量聚合酶链反应(qRT-PCR)检测了lncRNA XIST、miR-142-5p和血小板磷酸果糖激酶(PFKP)同工酶的表达。miR-142-5p与lncRNA XIST和PFKP之间的靶向关系通过皮尔逊相关分析、双荧光素酶报告实验和牵引实验得到了验证。功能实验分析了敲除lncRNA XIST对THP-1和U937细胞的影响和作用机制。与骨髓细胞相比,在AML中,lncRNA XIST和PFKP表达水平上调,miR-142-5p表达水平下调。进一步分析发现,lncRNA XIST与miR-142-5p靶向结合,而PFKP是miR-142-5p的靶基因。敲除lncRNA XIST能显著促进miR-142-5p的表达,从而下调PFKP在THP-1和U937细胞中的表达,同时抑制细胞增殖、细胞活力和细胞周期停滞,增加细胞凋亡。敲除 miR-142-5p 逆转了敲除 lncRNA XIST 对 AML 细胞的功能影响。总之,lncRNA XIST的下调可以通过调控miR-142-5p来影响AML的进展。
{"title":"Effect of lncRNA XIST on acute myeloid leukemia cells via miR-142-5p-PFKP axis.","authors":"Zhaozhi Jiang, Tingting Liu, Youhong Wang, Jiao Li, Lusheng Guo","doi":"10.1080/16078454.2024.2306444","DOIUrl":"10.1080/16078454.2024.2306444","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is the common blood cancer in hematopoietic system-related diseases and has a poor prognosis. Studies have shown that long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of a variety of diseases, including AML. However, the specific molecular mechanism remains unclear. Hence, the objective of this study was to investigate the effect and mechanism of lncRNA X inactive specific transcript (lncRNA XIST) on AML. To achieve our objective, some tests were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of lncRNA XIST, miR-142-5p and the platelet isoform of phosphofructokinase (PFKP). The targeting relationship between miR-142-5p and lncRNA XIST and PFKP was verified by Pearson correlation analysis, dual-luciferase reporter assay, and pull-down assay. Functional experiments were used to analyze the effect and mechanism of action of knocking down lncRNA XIST on THP-1 and U937 cells. Compared with bone marrow cells, lncRNA XIST and PFKP expression levels were up-regulated and miR-142-5p expression levels were down-regulated in AML. Further analysis revealed that lncRNA XIST targeted and bound to miR-142-5p, and PFKP was a target gene of miR-142-5p. Knockdown of lncRNA XIST significantly promoted miR-142-5p expression to down-regulate PFKP in THP-1 and U937 cells, while the cell proliferation, cell viability, and cell cycle arrest were inhibited and apoptosis was increased. Knockdown of miR-142-5p reversed the functional impact of lncRNA XIST knockdown on AML cells. In conclusion, down-regulation of lncRNA XIST can affect the progression of AML by regulating miR-142-5p.</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":"139671718","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}
Pub Date : 2024-12-01Epub Date: 2024-03-03DOI: 10.1080/16078454.2024.2324417
Mihee Kim, Seo-Yeon Ahn, TaeHyung Kim, Sung-Hoon Jung, Ga-Young Song, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Ju Heon Park, Myung-Geun Shin, Jae-Sook Ahn, Hyeoung-Joon Kim, Dennis Dong Hwan Kim
Objectives: This study aimed to evaluate the prognostic significance of the revised European LeukemiaNet (ELN)-2022 risk stratification model for 123 elderly acute myeloid leukemia (AML) patients treated with decitabine chemotherapy.
Results: Based on the ELN-2022 risk stratification, 15 (12.2%), 51 (41.5%), and 57 (46.3%) patients were classified as having favorable, intermediate, and high-risk AML, respectively. In comparison with the ELN-2017 risk stratification, the ELN-2022 risk stratification re-assigned 26 (21.1%) and three (2.4%) patients to the adverse and favorable risk groups, respectively. Survival analysis revealed distinctive overall survival (OS) outcomes among the ELN-2022 risk groups (6-month OS rate: 73.3%, 52.9%, and 47.7% for favorable, intermediate, and adverse risk, respectively; P = 0.101), with a parallel trend observed in the event-free survival (EFS) (6-month EFS rate: 73.3%, 52.9%, and 45.6% for favorable, intermediate, and adverse risk, respectively; P = 0.049). Notably, both OS and EFS in the favorable risk group were significantly superior in comparison to that of the adverse risk group (OS: P = 0.040, EFS: P = 0.030). Although the ELN-2022 C-index (0.559) was greater than the ELN-2017 C-index (0.539), the result was not statistically significant (P = 0.059). Based on the event net reclassification index, we consistently observed significant improvements in the ELN-2022 risk stratification for overall survival (0.21 at 6 months).
Conclusion: In conclusion, the revised ELN-2022 risk stratification model may have improved the risk classification of elderly AML patients treated with hypomethylating agents compared to the ELN-2017 risk stratification model.
{"title":"Prognostic analysis according to European LeukemiaNet 2022 risk stratification for elderly patients with acute myeloid leukemia treated with decitabine.","authors":"Mihee Kim, Seo-Yeon Ahn, TaeHyung Kim, Sung-Hoon Jung, Ga-Young Song, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, Ju Heon Park, Myung-Geun Shin, Jae-Sook Ahn, Hyeoung-Joon Kim, Dennis Dong Hwan Kim","doi":"10.1080/16078454.2024.2324417","DOIUrl":"10.1080/16078454.2024.2324417","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the prognostic significance of the revised European LeukemiaNet (ELN)-2022 risk stratification model for 123 elderly acute myeloid leukemia (AML) patients treated with decitabine chemotherapy.</p><p><strong>Results: </strong>Based on the ELN-2022 risk stratification, 15 (12.2%), 51 (41.5%), and 57 (46.3%) patients were classified as having favorable, intermediate, and high-risk AML, respectively. In comparison with the ELN-2017 risk stratification, the ELN-2022 risk stratification re-assigned 26 (21.1%) and three (2.4%) patients to the adverse and favorable risk groups, respectively. Survival analysis revealed distinctive overall survival (OS) outcomes among the ELN-2022 risk groups (6-month OS rate: 73.3%, 52.9%, and 47.7% for favorable, intermediate, and adverse risk, respectively; <i>P</i> = 0.101), with a parallel trend observed in the event-free survival (EFS) (6-month EFS rate: 73.3%, 52.9%, and 45.6% for favorable, intermediate, and adverse risk, respectively; <i>P</i> = 0.049). Notably, both OS and EFS in the favorable risk group were significantly superior in comparison to that of the adverse risk group (OS: <i>P</i> = 0.040, EFS: <i>P</i> = 0.030). Although the ELN-2022 C-index (0.559) was greater than the ELN-2017 C-index (0.539), the result was not statistically significant (<i>P</i> = 0.059). Based on the event net reclassification index, we consistently observed significant improvements in the ELN-2022 risk stratification for overall survival (0.21 at 6 months).</p><p><strong>Conclusion: </strong>In conclusion, the revised ELN-2022 risk stratification model may have improved the risk classification of elderly AML patients treated with hypomethylating agents compared to the ELN-2017 risk stratification model.</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":"140021553","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}
Pub Date : 2024-12-01Epub Date: 2024-03-12DOI: 10.1080/16078454.2024.2329378
Ying Chen, Zhe Chen, Junjie Cao, Li Lin, Jipeng Li
Objective: Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited.
Methods: In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis.
Results: Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses.
Conclusion: The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.
目的:多发性骨髓瘤(MM由于疾病的异质性,多发性骨髓瘤(MM)的临床表现、对治疗的反应和预后各不相同。有关非移植 MM 患者治疗期间免疫排斥状态与预后之间关系的数据十分有限:我们对 142 名 MM 患者进行了回顾性分析,研究了治疗期间免疫排斥状态与预后之间的关系。所有患者均接受了新型制剂治疗,未进行自体干细胞移植。一种、两种或三种未参与的免疫球蛋白(Igs)低于正常的最低阈值被用来识别免疫反应:结果:治疗期间免疫反应程度越严重的患者,无进展生存期(PFS)和总生存期(OS)越短。46.5%的患者存在严重和持续的免疫抑制(治疗期间至少有两种未涉及的 Igs 持续受到抑制),与治疗期间 Igs 完全或部分恢复正常的患者相比,预后更差。在至少获得完全缓解的患者中,重度和持续免疫反应低下患者的预后较差。此外,根据多变量分析,治疗期间严重和持续的免疫反应是PFS和OS的不良预后因素:结论:治疗期间的免疫排斥程度是非移植骨髓瘤患者生存率的随访指标,非移植骨髓瘤患者严重和持续的免疫排斥可能是预后不良的标志。
{"title":"Severe and continuous immunoparesis during induction or maintenance therapy in nontransplant patients with multiple myeloma is a sign of poor prognosis.","authors":"Ying Chen, Zhe Chen, Junjie Cao, Li Lin, Jipeng Li","doi":"10.1080/16078454.2024.2329378","DOIUrl":"10.1080/16078454.2024.2329378","url":null,"abstract":"<p><strong>Objective: </strong>Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited.</p><p><strong>Methods: </strong>In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis.</p><p><strong>Results: </strong>Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses.</p><p><strong>Conclusion: </strong>The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.</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":"140101500","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}
Pub Date : 2024-12-01Epub Date: 2024-01-07DOI: 10.1080/16078454.2023.2301633
Peiming Li, Xueru Ma, Guofei Huang
Thrombosis, a leading contributor to global health burden, is a complex process involving the interplay of various cell types, including vascular endothelial cells, platelets, and red blood cells. Oxidative stress, characterized by an overproduction of reactive oxygen species (ROS), can significantly impair the function of these cells, thus instigating a cascade of events leading to thrombus formation. In this review, we comprehensively explore the role of oxidative stress within these cells, and its mechanistic contribution to thrombogenesis, and the application of oxidative therapy in inhibiting thrombosis. By dissecting the intricacies of oxidative stress and its impact on thrombosis, we underscore its potential as a viable therapeutic target. Therefore, further research in this direction is warranted to enhance our understanding and management of thrombotic disorders.
{"title":"Understanding thrombosis: the critical role of oxidative stress.","authors":"Peiming Li, Xueru Ma, Guofei Huang","doi":"10.1080/16078454.2023.2301633","DOIUrl":"10.1080/16078454.2023.2301633","url":null,"abstract":"<p><p>Thrombosis, a leading contributor to global health burden, is a complex process involving the interplay of various cell types, including vascular endothelial cells, platelets, and red blood cells. Oxidative stress, characterized by an overproduction of reactive oxygen species (ROS), can significantly impair the function of these cells, thus instigating a cascade of events leading to thrombus formation. In this review, we comprehensively explore the role of oxidative stress within these cells, and its mechanistic contribution to thrombogenesis, and the application of oxidative therapy in inhibiting thrombosis. By dissecting the intricacies of oxidative stress and its impact on thrombosis, we underscore its potential as a viable therapeutic target. Therefore, further research in this direction is warranted to enhance our understanding and management of thrombotic disorders.</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":"139377489","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}