Experimental hematology最新文献_第4页

Remembering James Till, 1931-2025 纪念詹姆斯·蒂尔1931-2025

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-07-03 DOI: 10.1016/j.exphem.2025.104843

Norman Iscove, Alan Bernstein, Ron Worton

引用次数: 0

C-COUNT: a convolutional neural network–based tool for automated scoring of erythroid colonies C-COUNT：一种基于卷积神经网络的红系克隆自动评分工具。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-07-01 DOI: 10.1016/j.exphem.2025.104786

Rui Li, Ashley Winward, Logan R. Lalonde, Daniel Hidalgo, John P. Sardella, Yung Hwang, Aishwarya Swaminathan, Sean Thackeray, Kai Hu, Lihua Julie Zhu, Merav Socolovsky

{"title":"C-COUNT: a convolutional neural network–based tool for automated scoring of erythroid colonies","authors":"Rui Li, Ashley Winward, Logan R. Lalonde, Daniel Hidalgo, John P. Sardella, Yung Hwang, Aishwarya Swaminathan, Sean Thackeray, Kai Hu, Lihua Julie Zhu, Merav Socolovsky","doi":"10.1016/j.exphem.2025.104786","DOIUrl":"10.1016/j.exphem.2025.104786","url":null,"abstract":"<div><div>Despite advances in flow cytometry and single-cell transcriptomics, colony-formation assays (CFAs) remain an essential component in the evaluation of erythroid and hematopoietic progenitors. These assays provide functional information on progenitor differentiation and proliferative potential, making them a mainstay of hematology research and clinical diagnosis. However, the utility of CFAs is limited by the time-consuming and error-prone manual counting of colonies, which is also prone to bias and inconsistency. Here we present “C-COUNT,” a convolutional neural network–based tool that scores the standard colony-forming-unit-erythroid (CFU-e) assay by reliably identifying CFU-e colonies from images collected by automated microscopy and outputs both their number and size. We tested the performance of C-COUNT against three experienced scientists and find that it is equivalent or better in reliably identifying CFU-e colonies on plates that also contain myeloid colonies and other cell aggregates. We further evaluated its performance in the response of CFU-e progenitors to increasing erythropoietin concentrations and to a spectrum of genotoxic agents. We provide the C-COUNT code, a Docker image, a trained model, and training data set to facilitate its download, usage, and model refinement in other laboratories. The C-COUNT tool transforms the traditional CFU-e CFA into a rigorous and efficient assay with potential applications in high-throughput screens for novel erythropoietic factors and therapeutic agents.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"147 ","pages":"Article 104786"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980222","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 : 2025-07-01 DOI: 10.1016/S0301-472X(25)00115-8

引用次数: 0

Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis 基因调控复合体：它们在正常和恶性造血中的作用和调控。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-06-14 DOI: 10.1016/j.exphem.2025.104821

Gina Sangha , Brian J.P. Huntly

引用次数: 0

Advances in RARα fusion genes in acute promyelocytic leukemia 急性早幼粒细胞白血病RARα融合基因的研究进展。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-06-07 DOI: 10.1016/j.exphem.2025.104822

Ao Zhang , Shaowei Qiu

{"title":"Advances in RARα fusion genes in acute promyelocytic leukemia","authors":"Ao Zhang , Shaowei Qiu","doi":"10.1016/j.exphem.2025.104822","DOIUrl":"10.1016/j.exphem.2025.104822","url":null,"abstract":"<div><div>Retinoic acid receptor α (RARα) is a ligand-dependent transcription factor that dimerizes with retinoid X receptor α (RXRα) to activate target gene promoters, playing a critical role in normal hematopoiesis and granulocyte differentiation. The translocation of chromosomes 15 and 17 generates the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, the master driver of acute promyelocytic leukemia (APL). The PML-RARα oncoprotein exerts two major effects: transcriptional repression and disruption of promyelocytic leukemia (PML) function. The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has significantly improved the complete remission rate in APL, making it a highly treatable disease. However, resistance to ATRA/ATO and the emergence of variant fusion genes remain significant challenges to improving APL prognosis. This review provides an overview of the physiological role of retinoid nuclear receptor signaling in hematopoiesis, the pathological mechanisms of PML-RARα in APL, the pharmacologic effects of ATRA/ATO, and the variant translocations identified in APL. We aimed to provide innovative research perspectives and insights that may be applicable to other hematopoietic malignancies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"149 ","pages":"Article 104822"},"PeriodicalIF":2.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257689","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

Ex vivo modelling reveals low levels of CKS1 inhibition boost haematopoiesis via AKT/Foxo1 signalling 体外模型显示，低水平的CKS1抑制通过AKT/Foxo1信号传导促进造血。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-06-01 DOI: 10.1016/j.exphem.2025.104768

Juliana Fabiani Miranda , Adam Rogerson , Megan Guthrie , Kimrun Kaur , Emma Apperley , Mary Catherine Dunne , Navin Shridokar , Anjum Khan , William Grey

{"title":"Ex vivo modelling reveals low levels of CKS1 inhibition boost haematopoiesis via AKT/Foxo1 signalling","authors":"Juliana Fabiani Miranda , Adam Rogerson , Megan Guthrie , Kimrun Kaur , Emma Apperley , Mary Catherine Dunne , Navin Shridokar , Anjum Khan , William Grey","doi":"10.1016/j.exphem.2025.104768","DOIUrl":"10.1016/j.exphem.2025.104768","url":null,"abstract":"<div><div>Hematopoietic stem cells (HSCs) are rare cells residing at the top of the haematopoietic hierarchy capable of reconstituting all blood cell populations through their ability of self-renewal and differentiation. Their ability to maintain haematopoiesis can be majorly depleted by chemotherapeutic agents, leading to a long-term bone marrow injury. However, pre-clinical studies have focused on the acute effects of chemotherapy, leaving the lasting impact on healthy cells poorly understood. To study this, we combined rapid <em>ex vivo</em> models to study the long-term/late-stage effects of a cyclin-dependent kinase subunit 1 (CKS1) inhibitor. Inhibition of CKS1 has been shown to protect healthy HSCs from chemotherapy during acute myeloid leukaemia, and here we show a dose-dependent role of long-term CKS1 inhibition on haematopoiesis, either boosting B lymphopoiesis or ablating HSC proliferation capacity, dependent on the context. Mechanistically, low doses of the CKS1 inhibitor (CKS1i) affects AKT-Foxo1 signalling potentiating B-cell differentiation, but impairing HSC proliferation. These results reveal a novel role for CKS1 in boosting B lymphopoiesis and propose the use of rapid <em>ex vivo</em> models to investigate the long-term effects of chemotherapeutic treatments targeting HSCs with the potential of reducing late adverse effects.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"146 ","pages":"Article 104768"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751821","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 : 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