Experimental hematology最新文献_第8页

The inhibitory receptor PVRIG is dominantly expressed in the bone marrow of patients with multiple myeloma and its blockade enhances T-cell engager's immune activation 抑制受体PVRIG在多发性骨髓瘤患者骨髓中主要表达，其阻断可增强t细胞接合者的免疫激活。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-16 DOI: 10.1016/j.exphem.2024.104696

Masha Frenkel , Zoya Alteber , Ning Xu , Mingjie Li , Haiming Chen , Deborah Hayoun , Roy Zvi Granit , Gady Cojocaru , James Berenson , Eran Ophir

引用次数: 0

Understanding Human Oncogene Function and Cooperativity in Myeloid Malignancy Using iPSCs 利用iPSCs了解人类癌基因在髓系恶性肿瘤中的功能和协同性。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-12 DOI: 10.1016/j.exphem.2024.104697

Martina Sarchi , Sergei Doulatov

引用次数: 0

RNA methylation: where to from here for hematologic malignancies? RNA甲基化：血液恶性肿瘤的方向是什么？

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-06 DOI: 10.1016/j.exphem.2024.104694

Andrew Adel Guirguis

{"title":"RNA methylation: where to from here for hematologic malignancies?","authors":"Andrew Adel Guirguis","doi":"10.1016/j.exphem.2024.104694","DOIUrl":"10.1016/j.exphem.2024.104694","url":null,"abstract":"<div><div>RNA methylation and the machinery that regulates or “reads” its expression has recently been implicated in the pathogenesis of acute myeloid leukemia (AML) and other hematologic malignancies. Modulation of these epigenetic marks has started to become a reality as several companies around the world seek to leverage this knowledge therapeutically in the clinic. Although the bases of observed activity in AML have been described by numerous groups, the exact context in which these therapies will ultimately be used remains to be properly determined. While context is likely to be of great importance here, a more “global” mechanism of action might allow for more widespread applicability to multiple disease subtypes. In other areas such as the myelodysplastic and other preleukemic syndromes, data remain sparse. Ongoing work is needed to determine whether therapeutic modulation of RNA modifications is a viable and biologically plausible approach in these cases. Regardless of the outcomes, this is an exciting era for “epitranscriptomics” as we navigate a pathway forward. Here, I describe the current knowledge around RNA methylation and hematologic malignancies at the end of 2024 including some of the relevant questions that are yet to be answered.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104694"},"PeriodicalIF":2.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794364","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

IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-01 DOI: 10.1016/S0301-472X(24)00541-1

引用次数: 0

Cellular uptake of CPX-351 by scavenger receptor class B type 1–mediated nonendocytic pathway 细胞通过清道夫受体 B 类 1 型介导的非内皮细胞途径摄取 CPX-351。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-01 DOI: 10.1016/j.exphem.2024.104651

Hiroaki Araie, Naoko Hosono, Takahiro Yamauchi

{"title":"Cellular uptake of CPX-351 by scavenger receptor class B type 1–mediated nonendocytic pathway","authors":"Hiroaki Araie, Naoko Hosono, Takahiro Yamauchi","doi":"10.1016/j.exphem.2024.104651","DOIUrl":"10.1016/j.exphem.2024.104651","url":null,"abstract":"<div><div>The proper uptake of drugs in liposome formulations into target cells markedly impacts therapeutic efficacy. The protein corona (PC), formed by the adsorption of serum proteins onto the liposome surface, binds to specific surface receptors of target cells, influencing the uptake pathway. We investigated the uptake pathway into leukemia cells based on PC analysis of CPX-351, a liposome containing cytarabine and daunorubicin in a fixed 5:1 synergistic molar ratio. The PC of CPX-351 mixed with fetal bovine serum was analyzed by nanoflow liquid chromatography-tandem mass spectrometry. CPX-351 uptake in HL-60, K562, and THP-1 leukemia cell lines was measured by flow cytometry using daunorubicin fluorescence. The major components of CPX-351 PC include apolipoproteins A-I and A-II, which bind to scavenger receptor class B type 1 (SR-BI), a nonendocytic pathway that takes up only liposome contents. SR-BI was expressed in each cell, and its expression correlated with CPX-351 uptake. The uptake was significantly decreased by the inhibition of clathrin-mediated endocytosis and macropinocytosis. Additionally, blocks lipid transport-1 (BLT-1), a selective inhibitor of SR-BI, decreased the uptake; however, high-dose BLT-1 addition significantly increased the uptake, which was more strongly inhibited by macropinocytosis suppression compared with clathrin-mediated endocytosis. BLT-1 enhances the binding of SR-BI to liposomes in a dose-dependent manner. These findings indicate that the enhancement of binding between SR-BI and CPX-351 activates different pathways, such as macropinocytosis, distinct from CPX-351 alone. SR-BI may be a biomarker for CPX-351 therapy, and the combination of CPX-351 with high-dose BLT-1 may augment therapeutic efficacy.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104651"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A new era of functional experimentation in human hematopoiesis and leukemia research 人类造血和白血病研究功能实验的新时代。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-12-01 DOI: 10.1016/j.exphem.2024.104652

Thomas Köhnke, Yang Feng, Ravindra Majeti

引用次数: 0

Differential impact of CD34+ cell dose for different age groups in allogeneic hematopoietic cell transplantation for acute leukemia: a machine learning–based discovery cd34+ 细胞剂量对不同年龄组急性白血病异基因造血细胞移植的不同影响：基于机器学习的发现。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-23 DOI: 10.1016/j.exphem.2024.104684

Yiyang Qu , Hamed Shourabizadeh , Aravind Subramanian , Dionne M. Aleman , Louis-Martin Rousseau , Arjun D. Law , Auro Viswabandya , Fotios V. Michelis

{"title":"Differential impact of CD34+ cell dose for different age groups in allogeneic hematopoietic cell transplantation for acute leukemia: a machine learning–based discovery","authors":"Yiyang Qu , Hamed Shourabizadeh , Aravind Subramanian , Dionne M. Aleman , Louis-Martin Rousseau , Arjun D. Law , Auro Viswabandya , Fotios V. Michelis","doi":"10.1016/j.exphem.2024.104684","DOIUrl":"10.1016/j.exphem.2024.104684","url":null,"abstract":"<div><div>Allogeneic hematopoietic cell transplantation (allo-HCT) presents a potentially curative treatment for hematologic malignancies yet carries associated risks and complications. Continuous research focuses on predicting outcomes and identifying risk factors. Notably, the influence of CD34+ cell dose on overall survival (OS) has been the subject of numerous studies yielding contradictory results. We developed machine learning (ML) models to predict allo-HCT outcomes and, through the application of SHapley Additive exPlanations (SHAP), an explainable artificial intelligence (XAI) technique enabled the identification of new and clinically relevant feature-outcome relationships. In particular, we identified a clear interaction between CD34+ cell dose of peripheral blood stem cell (PBSC) grafts and patient age at allo-HCT for patients with acute leukemia. Results of multivariable analysis validated the interaction effect: in young patients with acute leukemia (aged ≤45 years), low dose of CD34+ cells (<4.3 × 10<sup>6</sup> CD34+/kg) was associated with better OS against high dose (≥7 ×10<sup>6</sup> CD34+/kg) (hazard ratio [HR], 0.38; <em>p</em> = 0.019), while for older patients with acute leukemia (>45 years), low CD34+ cell dose (<3.8 ×10<sup>6</sup> CD34+/kg) was associated with worse OS against high dose (≥6.1 ×10<sup>6</sup> CD34+/kg) (HR, 1.58; <em>p</em> = 0.033). In conclusion, our findings suggest that tailoring CD34+ cell dose by patient age may benefit patients with acute leukemia undergoing allo-HCT, while XAI showcases excellent proficiency in revealing such interactions.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"141 ","pages":"Article 104684"},"PeriodicalIF":2.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709054","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

Advice for effective leadership and hitting the ground running as a new group leader 为新任小组组长提供有效领导和顺利开展工作的建议。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-20 DOI: 10.1016/j.exphem.2024.104674

Lev M. Kats , Charles E. de Bock

引用次数: 0

Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia 阿伐曲波帕与标准免疫抑制疗法联合治疗重型再生障碍性贫血的有效性和安全性

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-05 DOI: 10.1016/j.exphem.2024.104670

Jianping Li , Weiru Liang , Huihui Fan , Kang Zhou , Yuan Li , Wenrui Yang , Liping Jing , Li Zhang , Lei Ye , Youzhen Xiong , Guangxin Peng , Yang Yang , Weiping Yuan , Jun Shi , Fengkui Zhang , Xin Zhao

{"title":"Efficacy and safety of avatrombopag in combination with standard immunosuppressive therapy for severe aplastic anemia","authors":"Jianping Li , Weiru Liang , Huihui Fan , Kang Zhou , Yuan Li , Wenrui Yang , Liping Jing , Li Zhang , Lei Ye , Youzhen Xiong , Guangxin Peng , Yang Yang , Weiping Yuan , Jun Shi , Fengkui Zhang , Xin Zhao","doi":"10.1016/j.exphem.2024.104670","DOIUrl":"10.1016/j.exphem.2024.104670","url":null,"abstract":"<div><div>Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. The addition of eltrombopag to immunosuppressive therapy (IST) improves the response rate, but its hepatotoxicity is concerning. Avatrombopag (AVA), a small-molecule thrombopoietin-receptor agonist without hepatotoxicity, has unknown efficacy in SAA treatment. This retrospective study assessed the efficacy and safety of AVA added to IST 42 SAA patients compared to a historical cohort of 84 patients receiving IST alone, using propensity score matching. The median age was 31.5 (6.0–67.0 years) years old in group A and 26 (16.0–45.0 years) years old in group B. At 3 months, group A showed higher complete response (CR) and overall response (OR) rates than group B (CR: 19.0% vs. 4.8%, <em>p</em> = 0.024; OR: 54.8% vs. 39.3%, <em>p</em> = 0.145). Higher CR and OR rates were also found at 6 months in group A than in group B (CR: 31.0% vs. 14.3%, <em>p</em> = 0.145; OR 71.4% vs. 51.2%, <em>p</em> = 0.048). In multivariate analysis of group A, a shorter interval from disease onset to antithymocyte globulin (ATG) treatment (≤6 months) (<em>p</em> = 0.005) predicted better responses rate at 6 months. Event-free survival was also improved in group A (60.7% vs. 49.6%). AVA was well-tolerated, with no hepatic injury observed during treatment, even in those with pre-existing hepatic impairment. The addition of AVA to IST improves both the response rate and response quality in patients with SAA while ensuring safety.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"140 ","pages":"Article 104670"},"PeriodicalIF":2.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes 研究骨髓衰竭和 MDS 易感综合征的可诱导多能干细胞模型。

IF 2.5 4区医学

Experimental hematology Pub Date : 2024-11-02 DOI: 10.1016/j.exphem.2024.104669

Sushree S. Sahoo , Majd Khiami , Marcin W. Wlodarski

{"title":"Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes","authors":"Sushree S. Sahoo , Majd Khiami , Marcin W. Wlodarski","doi":"10.1016/j.exphem.2024.104669","DOIUrl":"10.1016/j.exphem.2024.104669","url":null,"abstract":"<div><div>Induced pluripotent stem cells (iPSCs) have emerged as powerful tools for <em>in vitro</em> modeling of bone marrow failure (BMF) syndromes and hereditary conditions predisposing to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This review synthesizes recent advances in iPSC-based disease modeling for various inherited BMF/MDS disorders, including Fanconi anemia, dyskeratosis congenita, Diamond Blackfan anemia syndrome, Shwachman-Diamond syndrome, and severe congenital neutropenia as well as <em>GATA2, RUNX1, ETV6, ANKRD26, SAMD9, SAMD9L</em>, and <em>ADH5</em>/<em>ALDH2</em> syndromes. Although the majority of these iPSC lines are derived from patient cells, some are generated by introducing patient-specific mutations into healthy iPSC backgrounds, offering complementary approaches to disease modeling. The review highlights the ability of iPSCs to recapitulate key disease phenotypes, such as impaired hematopoietic differentiation, telomere dysfunction, and defects in DNA repair or ribosome biogenesis. We discuss how these models have enhanced our understanding of disease pathomechanisms, hematopoietic defects, and potential therapeutic approaches. Challenges in generating and maintaining disease-specific iPSCs are examined, particularly for disorders involving DNA repair. We emphasize the necessity of creating isogenic controls to elucidate genotype-phenotype relationships. Furthermore, we address limitations of current iPSC models, including genetic variability among iPSC clones derived from the same patient, and difficulties in achieving robust engraftment of iPSC-derived hematopoietic progenitor cells in mouse transplantation models. The review also explores future directions, including the potential of iPSC models for drug discovery and personalized medicine approaches. This review underscores the significance of iPSC technology in advancing our understanding of inherited hematopoietic disorders and its potential to inform novel therapeutic strategies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"143 ","pages":"Article 104669"},"PeriodicalIF":2.5,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0