血液科学(英文)Pub Date : 2024-01-10eCollection Date: 2024-01-01DOI: 10.1097/BS9.0000000000000176
Man Zhang, Di Liu, Yu Lan, Bing Liu, Zongcheng Li, Yanli Ni
{"title":"Hematopoietic stem cell heterogeneity in non-human primates revealed by five-lineage output bias analysis.","authors":"Man Zhang, Di Liu, Yu Lan, Bing Liu, Zongcheng Li, Yanli Ni","doi":"10.1097/BS9.0000000000000176","DOIUrl":"10.1097/BS9.0000000000000176","url":null,"abstract":"<p><p>Understanding hematopoietic stem cell (HSC) heterogeneity is crucial for treating malignant blood disorders. Compared with mice, we have limited knowledge of the heterogeneity of human HSCs. Fortunately, non-human primates (NHPs) have become the best animal models for studying human HSCs. Here, we employed a public dataset derived from NHP autologous bone marrow transplantation, and focused on a total of 820 HSC clones with reconstitution capacity of all available five lineages (granulocyte, monocyte, B cell, T cell, and natural killer cell) at two time points (11/12 and/or 42/43 months). Intriguingly, unsupervised clustering on these clones revealed six HSC subtypes, including a lymphoid/myeloid balanced (LM-balanced) subtype and five single-lineage-biased subtypes. We also observed that the subtypes of these HSC clones might change over time, and a given subtype could transition into any one of the other five subtypes, albeit with a certain degree of selectivity. Particularly, each of the six subtypes was more likely to turn into lymphoid-biased rather than myeloid-biased ones. Additionally, our five-lineage classification method exhibited strong correlation with traditional lymphoid/myeloid bias classification method. Specifically, our granulocyte- and monocyte-biased subtypes were predominantly attributed to α-HSCs, while LM-balanced, B cell-biased, and T cell-biased subtypes were primarily associated with β-HSCs. The γ-HSCs were composed of a small subset of B cell-biased and T cell-biased subtypes. In summary, our five-lineage classification identifies more finely tuned HSC subtypes based on lineage output bias. These findings enrich our understanding of HSC heterogeneity in NHPs and provide important insights for human research.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10781131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139426188","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}
血液科学(英文)Pub Date : 2024-01-10eCollection Date: 2024-01-01DOI: 10.1097/BS9.0000000000000178
Wen-Wen Li, Yong-Mei Zhang, Meng-Zhu Shen, Xiao-Dong Mo
{"title":"Efficacy and safety of letermovir prophylaxis for cytomegalovirus infection after hematopoietic stem cell transplantation.","authors":"Wen-Wen Li, Yong-Mei Zhang, Meng-Zhu Shen, Xiao-Dong Mo","doi":"10.1097/BS9.0000000000000178","DOIUrl":"10.1097/BS9.0000000000000178","url":null,"abstract":"<p><p>Letermovir is a specific inhibitor of cytomegalovirus (CMV) terminase complex. Several studies have reported that letermovir can effectively prevent CMV activation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of letermovir prophylaxis for CMV infection after allo-HSCT with a systemic review and meta-analysis. A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. PubMed and Embase databases were searched. A total of 28 studies were included. The incidence of CMV activation at 14 weeks after HSCT was 0.10 (95% confidence interval [CI], 0.06-0.18), which was 0.10 (95% CI, 0.04-0.21) and 0% in adult and children (2 studies were included and both of them were 0%). In addition, the incidence of CMV activation at 14 weeks after allo-HSCT was 0.11 (95% CI, 0.06-0.21) and 0.07 (only 1 study included), respectively, in retrospective and prospective studies. The incidence of CMV activation at 100 and 200 days after HSCT was 0.23 (95% CI, 0.16-0.33) and 0.49 (95% CI, 0.32-0.67), respectively. The incidence of CMV disease at 14 weeks and at 6 months after HSCT was 0.01 (95% CI, 0.01-0.02) and 0.03 (95% CI, 0.01-0.09), respectively. Thus, our systemic review and meta-analysis suggested that letermovir prophylaxis was safe and effective for CMV activation after allo-HSCT.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10781138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139426187","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}
血液科学(英文)Pub Date : 2023-11-02eCollection Date: 2023-10-01DOI: 10.1097/BS9.0000000000000172
Jun Du, Xiao-Ran Gu, Xiao-Xiao Yu, Yang-Jia Cao, Jian Hou
{"title":"Essential procedures of single-cell RNA sequencing in multiple myeloma and its translational value.","authors":"Jun Du, Xiao-Ran Gu, Xiao-Xiao Yu, Yang-Jia Cao, Jian Hou","doi":"10.1097/BS9.0000000000000172","DOIUrl":"10.1097/BS9.0000000000000172","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a malignant neoplasm characterized by clonal proliferation of abnormal plasma cells. In many countries, it ranks as the second most prevalent malignant neoplasm of the hematopoietic system. Although treatment methods for MM have been continuously improved and the survival of patients has been dramatically prolonged, MM remains an incurable disease with a high probability of recurrence. As such, there are still many challenges to be addressed. One promising approach is single-cell RNA sequencing (scRNA-seq), which can elucidate the transcriptome heterogeneity of individual cells and reveal previously unknown cell types or states in complex tissues. In this review, we outlined the experimental workflow of scRNA-seq in MM, listed some commonly used scRNA-seq platforms and analytical tools. In addition, with the advent of scRNA-seq, many studies have made new progress in the key molecular mechanisms during MM clonal evolution, cell interactions and molecular regulation in the microenvironment, and drug resistance mechanisms in target therapy. We summarized the main findings and sequencing platforms for applying scRNA-seq to MM research and proposed broad directions for targeted therapies based on these findings.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71524095","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}
血液科学(英文)Pub Date : 2023-11-02eCollection Date: 2023-10-01DOI: 10.1097/BS9.0000000000000173
Jia-Yi Wang, Liang Wang
{"title":"CAR-T cell therapy: Where are we now, and where are we heading?","authors":"Jia-Yi Wang, Liang Wang","doi":"10.1097/BS9.0000000000000173","DOIUrl":"10.1097/BS9.0000000000000173","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T-cell therapies have exhibited remarkable efficacy in the treatment of hematologic malignancies, with 9 CAR-T-cell products currently available. Furthermore, CAR-T cells have shown promising potential for expanding their therapeutic applications to diverse areas, including solid tumors, myocardial fibrosis, and autoimmune and infectious diseases. Despite these advancements, significant challenges pertaining to treatment-related toxic reactions and relapses persist. Consequently, current research efforts are focused on addressing these issues to enhance the safety and efficacy of CAR-T cells and reduce the relapse rate. This article provides a comprehensive overview of the present state of CAR-T-cell therapies, including their achievements, existing challenges, and potential future developments.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71524094","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}
血液科学(英文)Pub Date : 2023-09-08eCollection Date: 2023-10-01DOI: 10.1097/BS9.0000000000000171
Defu Zeng
{"title":"The opposite impact of Janus kinase inhibitor Ruxolitinib on the function of bone marrow mesenchymal stem cells and immune cells in acute GVHD recipients.","authors":"Defu Zeng","doi":"10.1097/BS9.0000000000000171","DOIUrl":"10.1097/BS9.0000000000000171","url":null,"abstract":"","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523550","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}
血液科学(英文)Pub Date : 2023-07-18eCollection Date: 2023-10-01DOI: 10.1097/BS9.0000000000000169
Ning Su, Yu Fang, Xu Chen, Xiaoqin Chen, Zhongjun Xia, Huiqiang Huang, Yi Xia, Panpan Liu, Xiaopeng Tian, Qingqing Cai
{"title":"Targeting P21-activated kinase suppresses proliferation and enhances chemosensitivity in T-cell lymphoblastic lymphoma.","authors":"Ning Su, Yu Fang, Xu Chen, Xiaoqin Chen, Zhongjun Xia, Huiqiang Huang, Yi Xia, Panpan Liu, Xiaopeng Tian, Qingqing Cai","doi":"10.1097/BS9.0000000000000169","DOIUrl":"10.1097/BS9.0000000000000169","url":null,"abstract":"<p><p>T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive non-Hodgkin lymphoma with a poor prognosis. P21-activated kinase (PAK) is a component of the gene expression-based classifier that can predict the prognosis of T-LBL. However, the role of PAK in T-LBL progression and survival remains poorly understood. Herein, we found that the expression of PAK1 was significantly higher in T-LBL cell lines (Jurkat, SUP-T1, and CCRF-CEM) compared to the human T-lymphoid cell line. Moreover, PAK2 mRNA level of 32 relapsed T-LBL patients was significantly higher than that of 37 cases without relapse (<i>P</i> = .012). T-LBL patients with high PAK1 and PAK2 expression had significantly shorter median RFS than those with low PAK1 and PAK2 expression (PAK1, <i>P</i> = .028; PAK2, <i>P</i> = .027; PAK1/2, <i>P</i> = .032). PAK inhibitors, PF3758309 (PF) and FRAX597, could suppress the proliferation of T-LBL cells by blocking the G1/S cell cycle phase transition. Besides, PF could enhance the chemosensitivity to doxorubicin in vitro and in vivo. Mechanistically, through western blotting and RNA sequencing, we identified that PF could inhibit the phosphorylation of PAK1/2 and downregulate the expression of cyclin D1, NF-κB and cell adhesion signaling pathways in T-LBL cell lines. These findings suggest that PAK might be associated with T-LBL recurrence and further found that PAK inhibitors could suppress proliferation and enhance chemosensitivity of T-LBL cells treated with doxorubicin. Collectively, our present study underscores the potential therapeutic effect of inhibiting PAK in T-LBL therapy.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61620349","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}
{"title":"Micheliolide exerts effects in myeloproliferative neoplasms through inhibiting STAT3/5 phosphorylation via covalent binding to STAT3/5 proteins.","authors":"Huijun Huang, Jinqin Liu, Lin Yang, Yiru Yan, Meng Chen, Bing Li, Zefeng Xu, Tiejun Qin, Shiqiang Qu, Liang Wang, Gang Huang, Yue Chen, Zhijian Xiao","doi":"10.1097/BS9.0000000000000168","DOIUrl":"10.1097/BS9.0000000000000168","url":null,"abstract":"<p><p>Ruxolitinib is a cornerstone of management for some subsets of myeloproliferative neoplasms (MPNs); however, a considerable number of patients respond suboptimally. Here, we evaluated the efficacy of micheliolide (MCL), a natural guaianolide sesquiterpene lactone, alone or in combination with ruxolitinib in samples from patients with MPNs, <i>JAK2</i>V617F-mutated MPN cell lines, and a <i>Jak2</i>V617F knock-in mouse model. MCL effectively suppressed colony formation of hematopoietic progenitors in samples from patients with MPNs and inhibited cell growth and survival of MPN cell lines in vitro. Co-treatment with MCL and ruxolitinib resulted in greater inhibitory effects compared with treatment with ruxolitinib alone. Moreover, dimethylaminomicheliolide (DMAMCL), an orally available derivative of MCL, significantly increased the efficacy of ruxolitinib in reducing splenomegaly and cytokine production in <i>Jak2</i>V617F knock-in mice without evident effects on normal hematopoiesis. Importantly, MCL could target the <i>Jak2</i>V617F clone and reduce mutant allele burden in vivo. Mechanistically, MCL can form a stable covalent bond with cysteine residues of STAT3/5 to suppress their phosphorylation, thus inhibiting JAK/STAT signaling. Overall, these findings suggest that MCL is a promising drug in combination with ruxolitinib in the setting of suboptimal response to ruxolitinib.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44607294","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}
血液科学(英文)Pub Date : 2023-07-05eCollection Date: 2023-07-01DOI: 10.1097/BS9.0000000000000166
Jiale Ma, Yan Gu, Yanhui Wei, Xuee Wang, Peixuan Wang, Chunhua Song, Zheng Ge
{"title":"Evaluation of new IPSS-Molecular model and comparison of different prognostic systems in patients with myelodysplastic syndrome.","authors":"Jiale Ma, Yan Gu, Yanhui Wei, Xuee Wang, Peixuan Wang, Chunhua Song, Zheng Ge","doi":"10.1097/BS9.0000000000000166","DOIUrl":"10.1097/BS9.0000000000000166","url":null,"abstract":"<p><p>A risk-adapted treatment strategy is of crucial importance in patients with myelodysplastic syndromes (MDS). Previous risk prognostic scoring systems did not integrate molecular abnormalities. The new IPSS-Molecular (IPSS-M) model, combing genomic profiling with hematologic and cytogenetic parameters, was recently developed to evaluate the associations with leukemia-free survival (LFS), leukemic transformation, and overall survival (OS). However, it has not yet been widely validated in clinics. This study aims to further validate the prognostic power of IPSS-M based on real-world data and to compare the prognostic value of different scoring systems in patients with MDS. IPSS-M Web calculator was used to calculate a tailored IPSS-M score of the enrolled patient (N = 255), and the risk category was defined correspondingly. We next compared the IPSS-M prognostic power to that of IPSS, IPSS-R, and WPSS. We found that IPSS-M risk classification was statistically significant for 3-year OS and LFS. Compared with other tools, IPSS-M was superior in sensitivity and accuracy for 3-year OS and LFS. The mapping C-index between IPSS-R and IPSS-M categories resulted in improved discrimination across the OS, but not LFS and leukemic transformation. The result of different treatment options indicated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) can result in a better OS than those without allo-HSCT. In conclusion, IPSS-M was a valuable tool for risk stratification compared with other risk prognostic scoring systems. However, more studies should be conducted to explore the appropriate treatment options for different groups stratified by IPSS-M.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006856","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}