Experimental hematology最新文献_第2页

IFC Editorial Board IFC编委会

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-06-01 DOI: 10.1016/S0301-472X(25)00094-3

引用次数: 0

Balancing hematopoietic stem cell self-renewal and differentiation activities throughout ontogeny and aging 造血干细胞自我更新和分化活动在个体发育和衰老过程中的平衡。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-31 DOI: 10.1016/j.exphem.2025.104820

Masayuki Yamashita , Jingjing Li , Vu L. Tran , Myriam L.R. Haltalli , Shannon McKinney-Freeman , Toshio Suda

引用次数: 0

Peposertib suppresses generation of FLT3-internal tandem duplication formed by contralateral double nicks Peposertib抑制由对侧双切口形成的flt3 -内部串联重复的产生。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-31 DOI: 10.1016/j.exphem.2025.104819

Shota Yoshida , Masahiro Onozawa , Shota Yokoyama , Toshihiro Matsukawa , Hideki Goto , Shinsuke Hirabayashi , Takeshi Kondo , Daigo Hashimoto , Yasuhito Onodera , Takanori Teshima

{"title":"Peposertib suppresses generation of FLT3-internal tandem duplication formed by contralateral double nicks","authors":"Shota Yoshida , Masahiro Onozawa , Shota Yokoyama , Toshihiro Matsukawa , Hideki Goto , Shinsuke Hirabayashi , Takeshi Kondo , Daigo Hashimoto , Yasuhito Onodera , Takanori Teshima","doi":"10.1016/j.exphem.2025.104819","DOIUrl":"10.1016/j.exphem.2025.104819","url":null,"abstract":"<div><div>Fms-like tyrosine kinase 3-internal tandem duplication (<em>FLT3</em>-ITD) is the most frequent gene mutation in acute myeloid leukemia. The consequences of <em>FLT3</em>-ITD have been analyzed in detail; however, the molecular mechanisms underlying the generation of <em>FLT3-ITD</em> remain to be elucidated. We analyzed <em>FLT3</em>-ITDs in clinical samples using deep sequencing and identified not only oligoclonal ITDs but also rare deletion clones clustered at the palindrome-like sequence at <em>FLT3</em> exon 14. We hypothesized that <em>FLT3</em> exon 14 is genetically unstable due to the palindrome-like sequence at the region and that genomic damage at the site initiates <em>FLT3</em>-ITD formation. We used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 to induce DNA damage for creating artificial <em>FLT3</em>-ITDs in human and mouse cell lines. We found that double nicks on the adjacent contralateral strand most efficiently generate ITDs. The artificial ITDs resembled clinical ITDs in the length distribution and characteristics at the joint. We further compared the inhibitory effects of olaparib and peposertib, specific inhibitors of single-strand break (SSB) and double-strand break (DSB) repair, respectively. Peposertib remarkably reduced ITD formation, but olaparib did not affect the mutation pattern. The findings indicated that nonhomologous end joining has a crucial role in the generation of ITDs. Our data shed light to the new role of peposertib, which potentially suppresses the generation of de novo <em>FLT3</em>-ITDs caused by mis-repair events of the DNA damages in a clinical course.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"149 ","pages":"Article 104819"},"PeriodicalIF":2.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208073","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

FOXP1 contributes to murine hematopoietic stem cell functionality FOXP1有助于小鼠造血干细胞的功能。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-29 DOI: 10.1016/j.exphem.2025.104815

Françoise Levavasseur , Samia Oussous , Alessandro Framarini , Ismael Boussaid , Panhong Gou , Zubaidan Tuerdi , Iman Litchy Boueya , Helyette Hoffner , Marta De Almeida , Morgane Le Gall , Haley Tucker , Stéphane Giraudier , Didier Bouscary , Michaela Fontenay , Diana Passaro , Isabelle Dusanter-Fourt , Evelyne Lauret

{"title":"FOXP1 contributes to murine hematopoietic stem cell functionality","authors":"Françoise Levavasseur , Samia Oussous , Alessandro Framarini , Ismael Boussaid , Panhong Gou , Zubaidan Tuerdi , Iman Litchy Boueya , Helyette Hoffner , Marta De Almeida , Morgane Le Gall , Haley Tucker , Stéphane Giraudier , Didier Bouscary , Michaela Fontenay , Diana Passaro , Isabelle Dusanter-Fourt , Evelyne Lauret","doi":"10.1016/j.exphem.2025.104815","DOIUrl":"10.1016/j.exphem.2025.104815","url":null,"abstract":"<div><div>Transcription factor forkhead box P1 (FOXP1) is a key regulator of immune cell functions. We have shown that FOXP1 contributes to the expansion of human hematopoietic stem/progenitor cell (HSPC) and acute myeloid leukemia cells. Here, we investigated the role of FOXP1 in early adult mouse hematopoiesis in vivo. We showed that loss of hematopoietic-specific FOXP1 expression leads to attrition of the hematopoietic stem cell (HSC) and multipotent progenitor (MPP)-1 compartment in parallel with enhancement of myeloid-biased MPP3 in adult bone marrow and fetal liver. Transplantation experiments confirmed that FOXP1-deficient bone marrow had an intrinsic reduced HSC compartment. FOXP1-deficient MPP compartments also showed enhanced proliferation with G0 phase reduction. Transcriptome analyses revealed that FOXP1-deficient HSC exhibited reduced stemness and enhanced expression of cell proliferation pathways. Thus, our current results revealed that FOXP1 plays a critical role in early murine hematopoiesis by maintaining HSCs, limiting the expansion of all MPP compartments, and restricting early myeloid commitment in vivo.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"149 ","pages":"Article 104815"},"PeriodicalIF":2.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191700","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

Intra-bone marrow diversity of endothelial cells and its impact on hematopoietic stem cell development and maintenance 骨髓内内皮细胞多样性及其对造血干细胞发育和维持的影响。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-05-26 DOI: 10.1016/j.exphem.2025.104817

Shota Shimizu, Yoshiaki Kubota

引用次数: 0

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 B 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 B 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}

引用次数: 0

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