Experimental hematology最新文献_第2页

Transcription factors that define the epigenome structures and transcriptomes in microglia. 定义小胶质细胞表观基因组结构和转录组的转录因子。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-25 DOI: 10.1016/j.exphem.2025.104814

Keita Saeki, Keiko Ozato

引用次数: 0

Cell-extrinsic factors contribute toward myeloid-biased expansion in Tet2-mutant clonal hematopoiesis 细胞外源性因素有助于tet2突变克隆造血中骨髓偏向性扩张。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-22 DOI: 10.1016/j.exphem.2025.104816

Aishwarya Krishnan , Linde A. Miles , Grant A. Challen

引用次数: 0

NAMPT-mediated deacetylation of HCLS1 protein promotes clonogenic growth of pediatric CML cells. nampt介导的HCLS1蛋白去乙酰化促进儿童CML细胞的克隆生长。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-10 DOI: 10.1016/j.exphem.2025.104801

Bardia Samareh, Olga Klimenkova, Narges Aghaallaei, Lijuan Cheng, Andrew Zikic, Houra Loghmani, Ivan Tesakov, Patrick Müller, Meinolf Suttorp, Karl Welte, Julia Skokowa, Tatsuya Morishima

{"title":"NAMPT-mediated deacetylation of HCLS1 protein promotes clonogenic growth of pediatric CML cells.","authors":"Bardia Samareh, Olga Klimenkova, Narges Aghaallaei, Lijuan Cheng, Andrew Zikic, Houra Loghmani, Ivan Tesakov, Patrick Müller, Meinolf Suttorp, Karl Welte, Julia Skokowa, Tatsuya Morishima","doi":"10.1016/j.exphem.2025.104801","DOIUrl":"10.1016/j.exphem.2025.104801","url":null,"abstract":"<p><p>Pediatric chronic myeloid leukemia (CML) is a rare hematologic malignancy with biological features that differ from that of adult patients. In pediatric patients with CML the burden of tumor cells is higher resulting in a delayed achievement of deep molecular response (DMR) upon treatment with tyrosine kinase inhibitors (TKIs, e.g., imatinib) than what has been reported in adults. Therefore, the probability to develop resistance to TKIs in children with CML is higher than in adults due to much longer exposure to TKIs. Moreover, in children with CML, long-term treatment with imatinib causes hematologic and nonhematologic toxicities. Improvements of CML therapy in pediatric patients based on the targeting of hematopoiesis-specific BCR::ABL1 downstream effectors are needed. Here, we report elevated levels of the nicotinamide phosphoribosyltransferase (NAMPT) in mononuclear cells of pediatric patients with chronic phase CML (CP-CML) and in blastic phase CML cell lines. NAMPT inhibition abrogated in vitro clonogenic capacity and proliferation of CML cells. NAMPT deacetylates and activates the hematopoietic-specific lyn-substrate 1 (HCLS1) protein, which is essential for the proliferation of CML cells. Moreover, IL1RAP - a marker of myeloid leukemia-initiating cells - and LEF-1 - a transcription factor of Wnt signaling - are downstream targets of NAMPT/HCLS1 pathway. Together, our results reveal new treatment avenues of pediatric patients with CML by targeting NAMPT-mediated deacetylation of the hematopoietic-specific HCLS1 protein.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104801"},"PeriodicalIF":2.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970608","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

FAM210B regulates iron homeostasis and sex-specific responses in stress erythropoiesis. FAM210B调节应激红细胞生成中的铁稳态和性别特异性反应。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-10 DOI: 10.1016/j.exphem.2025.104797

Mark Perfetto, Muhammad Ishfaq, Aiden Mohideen, Catherine M Rondelli, Samantha Gillis, Jesus Tejero, Amber N Stratman, Rebecca Riggins, Yvette Y Yien

{"title":"FAM210B regulates iron homeostasis and sex-specific responses in stress erythropoiesis.","authors":"Mark Perfetto, Muhammad Ishfaq, Aiden Mohideen, Catherine M Rondelli, Samantha Gillis, Jesus Tejero, Amber N Stratman, Rebecca Riggins, Yvette Y Yien","doi":"10.1016/j.exphem.2025.104797","DOIUrl":"10.1016/j.exphem.2025.104797","url":null,"abstract":"<p><p>Iron is required for redox homeostasis but poses toxicity risks due to its redox activity. Erythropoiesis hence requires tight regulation of iron utilization for hemoglobin synthesis. The requirement for iron in erythropoiesis has necessitated the evolution of mechanisms to handle the iron required for hemoglobinization. FAM210B was identified as a regulator of mitochondrial iron import and heme synthesis in erythroid cell culture and zebrafish models. Here, we demonstrate that although FAM210B is required for erythroid differentiation and heme synthesis under standard cell culture conditions, holotransferrin supplementation was sufficient to chemically complement the iron-deficient phenotype. To investigate the role of FAM210B in erythropoiesis, we used knockout mice. Although Fam210b<sup>-/-</sup> mice were viable and did not exhibit overt erythropoietic defects in the bone marrow, the male mice exhibited an increase in serum transferrin, suggesting sex-specific alterations in systemic iron sensing. On phlebotomy-induced stress erythropoiesis, Fam210b<sup>-/-</sup> mice exhibited differences in serum transferrin levels, and more starkly, had markedly smaller spleens, indicating defects in stress response. Fam210b<sup>-/-</sup> males had defects in neutrophil and monocyte numbers, as well as decreased erythroid progenitor numbers during erythropoietic stress. Together, our findings show that Fam210b plays a key role in the splenic response to erythropoietic stress. Our findings reveal a critical role for FAM210B in mediating splenic stress erythropoiesis and suggest it may act as a sex-specific regulator, potentially linked to androgen signaling.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104797"},"PeriodicalIF":2.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991599","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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Effect of peritransplant measurable residual disease clearance in patients with myelodysplastic neoplasm: a referral center experience. 骨髓增生异常肿瘤患者移植期可测量残留疾病清除率的影响转诊中心经验：MDS患者hsct周MRD清除的影响。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-10 DOI: 10.1016/j.exphem.2025.104799

Kittika Poonsombudlert, Sarah Mott, Ratdanai Yodsuwan, Andrew Vegel, Aditya Ravindra, Prajwal Dhakal, Grerk Sutamtewagul, Margarida Magalhaes-Silverman

{"title":"Effect of peritransplant measurable residual disease clearance in patients with myelodysplastic neoplasm: a referral center experience.","authors":"Kittika Poonsombudlert, Sarah Mott, Ratdanai Yodsuwan, Andrew Vegel, Aditya Ravindra, Prajwal Dhakal, Grerk Sutamtewagul, Margarida Magalhaes-Silverman","doi":"10.1016/j.exphem.2025.104799","DOIUrl":"10.1016/j.exphem.2025.104799","url":null,"abstract":"<p><p>Periallogeneic stem cell transplant (peri-HSCT) measurable residual disease (MRD) is increasingly recognized as a prognostic marker. However, the MRD status in myelodysplastic neoplasm (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), are less well-established compared with B-acute lymphoblastic leukemia. We reviewed the charts of adults who underwent HSCT for MDS or MDS/MPN between 2012 and 2023 and evaluated the effect of pre-HSCT MRD status on relapse-free survival (RFS) and overall survival (OS). A conditional analysis of outcomes based on day+90 post-HSCT MRD status was also performed. There were 38 and 55 patients in MRD- and MRD+ cohorts respectively. Baseline patient characteristics, including age, Revised and Molecular International Prognostic Scores (IPSS-R and IPSS-M), and HSCT-related factors were similar between MRD+ and MRD- cohort. The MRD+ cohort had inferior RFS (HR: 1.84, 95% CI: 1.09-3.12, p = 0.02) but a statistically significant difference in OS was not evidenced (HR: 1.52, 95% CI: 0.88-2.61, p = 0.14). After adjusting for % blasts at diagnosis, and conditioning intensity, patients with MRD+ were found to be at 1.92 times increased risk of relapse or death (95% CI: 1.12-3.28, p = 0.02). Additionally, increasing IPSS-M score was associated with poorer RFS (HR: 1.27, 95% CI: 1.01-1.59, p = 0.04) and OS (HR: 1.52, 95% CI: 1.20-1.91, p < 0.01). Among patients who were alive and in remission until day +90 post-HSCT, the pre-HSCT MRD status did not confer a statistically significant difference in RFS and OS if they became MRD- by day +90 post-HSCT. Pre- and peri-HSCT MRD testing could offer valuable prognostic information in patients with MDS and MDS/MPN.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"104799"},"PeriodicalIF":2.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999232","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

Vesicle-mediated information transfer in cardiovascular cell differentiation 心血管细胞分化中囊泡介导的信息传递。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-09 DOI: 10.1016/j.exphem.2025.104800

Jun K. Yamashita

{"title":"Vesicle-mediated information transfer in cardiovascular cell differentiation","authors":"Jun K. Yamashita","doi":"10.1016/j.exphem.2025.104800","DOIUrl":"10.1016/j.exphem.2025.104800","url":null,"abstract":"<div><div>Extracellular vesicles (EVs)—including exosomes, microvesicles, and apoptotic bodies—are membrane-bound carriers of diverse molecular cargo such as nucleic acids, proteins, and lipids. They are increasingly recognized as critical mediators of information transfer during cardiovascular cell differentiation, development, diseases, and regeneration. Emerging evidence highlights the capacity of EV-encapsulated microRNAs (miRNAs) to drive cardiomyocyte differentiation and support angiogenesis. We recently discovered a novel EV-mediated mechanism termed “phenotypic synchronization of cells” (PSyC). When protein kinase A (PKA) is activated in pluripotent stem cells, the speed of mesodermal differentiation increases, partly through elevated EV-encapsulated miR-132. miR-132, transferred to neighboring cells with EVs, reactivates PKA signaling in recipient cells, synchronizing differentiation stages. Additionally, ex vivo assays reveal that EVs derived from PKA-activated cells can induce cardiomyocyte differentiation in early-stage embryos, underscoring the potency of EV-based signaling in shaping cardiovascular phenotypes. We recently uncovered a novel modality of vesicle-mediated intercellular communication, named direct intercellular vesicle exchange (DIVE), a distinct pathway enabling rapid and direct vesicle transfer between adjacent cells. By facilitating the direct traverse of nucleic acid-laden vesicles across the plasma membrane, DIVE may reinforce conventional EV-based signaling in cardiovascular differentiation. Together, these findings underscore the fundamental role of vesicle-mediated information exchange in orchestrating cardiac and vascular cell fates. Exploiting vesicle-mediated communication may open new avenues in regenerative medicine, disease modeling, and therapeutic interventions aimed at modulating cardiovascular cell function.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"148 ","pages":"Article 104800"},"PeriodicalIF":2.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976599","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

Ontogeny, dynamics, and characteristics of neutrophils during the perinatal period 围产期中性粒细胞的个体发生、动态和特征。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-09 DOI: 10.1016/j.exphem.2025.104798

Ryo Ishiwata

{"title":"Ontogeny, dynamics, and characteristics of neutrophils during the perinatal period","authors":"Ryo Ishiwata","doi":"10.1016/j.exphem.2025.104798","DOIUrl":"10.1016/j.exphem.2025.104798","url":null,"abstract":"<div><div>This review examined the dynamic development and unique characteristics of neutrophils during the perinatal period, a critical window when the immune system undergoes rapid reprogramming, based on the mouse studies. In the mouse fetal liver—the primary hematopoietic niche before birth—hematopoietic stem cells and progenitor cells expand in parallel, with granulocyte–monocyte progenitors preferentially differentiating into neutrophils during late gestation. This process, partly driven by granulocyte colony-stimulating factor (G-CSF), substantially increases the number of neutrophils, preparing the neonates for microbial challenges after birth. After birth, there is a surge in circulating neutrophils, likely due to the mobilization of neutrophils from the liver, followed by a microbiota-dependent activation of granulopoiesis in the bone marrow. In addition to their antimicrobial functions, neonatal neutrophils exhibit immunomodulatory characteristics, such as reduced proinflammatory signaling and diminished neutrophil extracellular trap formation. These traits may contribute to tolerance to the microbes and help mitigate excessive inflammation. Finally, unresolved issues related to the phenotypic diversity and precise physiological roles of neutrophils during the perinatal period are addressed, highlighting the need for further research.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"148 ","pages":"Article 104798"},"PeriodicalIF":2.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965069","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

Notch1 activation and inhibition in T-cell acute lymphoblastic leukemia subtypes Notch1在T细胞急性淋巴细胞白血病亚型中的激活和抑制作用。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-08 DOI: 10.1016/j.exphem.2025.104771

Jiawen Lu , Xiuhua Xue , Haitao Wang , Ying Hao , Qiong Yang

引用次数: 0

A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells 在kmt2a重排的儿童t细胞急性淋巴细胞白血病细胞中，一种独特的替代mRNA剪接谱鉴定了致癌CD44转录物变体3

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/j.exphem.2025.104712

Amanda Ramilo Amor , Sabina Enlund , Indranil Sinha , Qingfei Jiang , Ola Hermanson , Anna Nilsson , Shahrzad Shirazi Fard , Frida Holm

{"title":"A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells","authors":"Amanda Ramilo Amor , Sabina Enlund , Indranil Sinha , Qingfei Jiang , Ola Hermanson , Anna Nilsson , Shahrzad Shirazi Fard , Frida Holm","doi":"10.1016/j.exphem.2025.104712","DOIUrl":"10.1016/j.exphem.2025.104712","url":null,"abstract":"<div><div>T-cell acute lymphoblastic leukemia (T-ALL), which constitutes of 10–15% of all pediatric acute lymphoblastic leukemia (ALL) cases, is known for its complex pathology due to pervasive genetic and chromosomal abnormalities. Although most children are successfully cured, chromosomal rearrangements involving the KMT2A gene is considered a poor prognostic factor. In a cohort of 171 pediatric T-ALL samples, we have studied differences in gene and splice variant patterns in KMT2A-rearranged (KMT2A-r) T-ALL compared with KMT2A-negative (KMT2A-wt) T-ALL samples. Our results have identified a distinct gene expression and splice variant expression pattern in pediatric KMT2A-r patient samples including significant expression of splicing regulatory markers ESRP1 and MBNL3. Additionally, the prosurvival long transcript variant of BCL2 were upregulated in KMT2A-r compared with KMT2A-wt T-ALL samples. Lastly, increased levels of activating methylation in the promoter region of CD44 were identified followed by an upregulation of the oncogenic transcript variant CD44v3 in KMT2A-r T-ALL. Together, this suggests that CD44v3 could play a potential role as gene expression–based risk stratification of KMT2A-r T-ALL and could possibly serve as a therapeutic target using splicing modulators.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104712"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964310","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

Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells 多能干细胞体外生成和扩增人造血干细胞的优势和挑战。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-01 DOI: 10.1016/j.exphem.2025.104752

Min Ding , Yu Lu , Quan-Kai Lei , Yun-Wen Zheng

{"title":"Advantages and challenges of ex vivo generation and expansion of human hematopoietic stem cells from pluripotent stem cells","authors":"Min Ding , Yu Lu , Quan-Kai Lei , Yun-Wen Zheng","doi":"10.1016/j.exphem.2025.104752","DOIUrl":"10.1016/j.exphem.2025.104752","url":null,"abstract":"<div><div>Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogens, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges. By enabling the generation of hematopoietic stem cells (HSCs) and blood cells in vitro, PSCs open pathways to address the limitations of traditional HSC sources. Self-induced or gene-edited PSCs from patients may provide an accessible and personalized option for clinical applications. In this review, we examine the current protocols for differentiating PSCs into HSCs and blood cells, highlighting their benefits and shortcomings. Despite advancements in this field, two primary challenges persist: low differentiation efficiency and difficulties in isolating and enriching functional HSCs. These problems make it difficult to obtain HSCs for long-term survival. Thus, we propose innovative strategies and potential improvements including induction scheme optimization, reprogramming, and cell fate tracking. Future research should prioritize the development of efficient and reliable differentiation protocols for PSCs to obtain more functional HSCs. Additionally, establishing effective methods for enriching functional HSCs and blood cells will be critical for optimizing their use in clinical applications. These efforts hold the promise of overcoming current limitations and advancing the therapeutic potential of PSC-derived blood cells.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"145 ","pages":"Article 104752"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630286","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