Experimental hematology最新文献_第2页

Bone marrow niches for hematopoietic stem cells in homeostasis and aging

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-18 DOI: 10.1016/j.exphem.2025.104749

Taichi Nakatani, Takashi Nagasawa

{"title":"Bone marrow niches for hematopoietic stem cells in homeostasis and aging","authors":"Taichi Nakatani, Takashi Nagasawa","doi":"10.1016/j.exphem.2025.104749","DOIUrl":"10.1016/j.exphem.2025.104749","url":null,"abstract":"<div><div>Among various types of candidate cells, including osteoblasts and Nestin<sup>+</sup> periarteriolar cells, several lines of histological and genetic evidence have demonstrated that the single population of mesenchymal stem cells, termed CXC chemokine ligand 12 (CXCL12)–abundant reticular (CAR) cells, which overlap strongly with leptin receptor–expressing (LepR<sup>+</sup>) cells, is the major cellular component of niches for hematopoietic stem cells (HSCs) and hematopoiesis in the bone marrow (BM). Expression of p16, a marker for senescent cells, and interleukin (IL)-1β and γH2AX foci, a marker for DNA damage, were increased in CAR/LepR<sup>+</sup> cells and osteoblasts with age. However, the most striking phenotype of aging in the human BM is yellow marrow, which consists predominantly of adipocytes, causing the decreased volume of the principal site of hematopoiesis probably with the decreased numbers of HSCs in the total body. BM adipocytes are derived from CAR/LepR<sup>+</sup> cells and act as negative or positive regulators of HSCs during homeostasis and myelosuppressive condition. Therefore, a fundamental question is how a portion of BM CAR/LepR<sup>+</sup> cells differentiate into adipocytes during aging. Many rounds of inflammatory stress induced yellow marrow in mice. On the other hand, type H vessels found in the metaphysis and peripheral nerves running along the arteries were markedly reduced in the marrow of aged mice, which might affect HSCs and/or their niche cells. Understanding the cellular and molecular function of aged HSC niches could enable pharmacological regulation of niche functions to facilitate control of disease caused by BM aging.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104749"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467483","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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In Memoriam: Prof. Vittorio Rizzoli, The visionary who built experimental hematology in Italy

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-17 DOI: 10.1016/j.exphem.2025.104735

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Preconditioning intervention prior to allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-12 DOI: 10.1016/j.exphem.2025.104746

Takayoshi Tachibana , Akihiko Izumi , Shota Arai , Takaaki Takeda , Natsuki Hirose , Yotaro Tamai , Shuku Sato , Chizuko Hashimoto , Katsumichi Fujimaki , Ryuji Ishii , Hirotaka Sakai , Etsuko Yamazaki , Yasuyuki Inoue , Masatsugu Tanaka , Hideaki Nakajima

{"title":"Preconditioning intervention prior to allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia","authors":"Takayoshi Tachibana , Akihiko Izumi , Shota Arai , Takaaki Takeda , Natsuki Hirose , Yotaro Tamai , Shuku Sato , Chizuko Hashimoto , Katsumichi Fujimaki , Ryuji Ishii , Hirotaka Sakai , Etsuko Yamazaki , Yasuyuki Inoue , Masatsugu Tanaka , Hideaki Nakajima","doi":"10.1016/j.exphem.2025.104746","DOIUrl":"10.1016/j.exphem.2025.104746","url":null,"abstract":"<div><div>The outcomes of patients with high-risk acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HCT) remain poor despite many attempts at developing therapeutic strategies. Preconditioning interventions (PCIs) have been applied to patients with high-risk AML to reduce the disease burden before starting the conditioning regimen. A single-center retrospective study was performed to evaluate the safety and efficacy of PCI in allograft patients with high-risk AML. Thirty-three patients with a median age of 57 (16–70) years were included to the entire cohort. Among various PCI regimens, venetoclax plus azacitidine was administered to 12 patients. The median drug withdrawal day was 0 days (range, 0–12) for low-intensity PCIs and 12 days (range, 8–14) for high-intensity PCIs. With no grade 3 nonhematological adverse events during PCIs, the median blast fraction in the bone marrow before and after PCIs decreased from 12.4% to 2.1% (<em>p</em> = 0.001). Excluding three patients with early complication-related deaths, all 30 patients achieved engraftment within a median of 30 days. The overall survival, cumulative incidence of relapse, and nonrelapse mortality (NRM) rates at 2 years were 67.1%, 23.9%, and 8.8%, respectively. The cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) at 100 days and chronic GVHD at 2 years were 32.4% and 23.5%, respectively. PCI may be safe and effective in promoting engraftment and reducing the risk of disease relapse without increasing the risk of NRM. Further clinical trials are warranted to establish appropriate PCI strategies.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104746"},"PeriodicalIF":2.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425392","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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Charting new paths in experimental hematology: Revitalizing the editorial board and upcoming initiatives

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-11 DOI: 10.1016/j.exphem.2025.104745

Keisuke Ito

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CBX7 inhibitors affect H3K9 methyltransferase-regulated gene repression in leukemic cells CBX7抑制剂影响白血病细胞中H3K9甲基转移酶调节的基因抑制。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104691

Anne P. de Groot , Huong Nguyen , Jacobine S. Pouw , Ellen Weersing , Albertina Dethmers-Ausema , Gerald de Haan

{"title":"CBX7 inhibitors affect H3K9 methyltransferase-regulated gene repression in leukemic cells","authors":"Anne P. de Groot , Huong Nguyen , Jacobine S. Pouw , Ellen Weersing , Albertina Dethmers-Ausema , Gerald de Haan","doi":"10.1016/j.exphem.2024.104691","DOIUrl":"10.1016/j.exphem.2024.104691","url":null,"abstract":"<div><div>The epigenome of leukemic cells is dysregulated, and genes required for cell cycle arrest and differentiation may become repressed, which contributes to the accumulation of undifferentiated malignant blood cells. Here, we show that the Polycomb group protein CBX7 can interact with H3K9 methyltransferases EHMT1/2 and SETDB1. We aimed to assess whether combined interfering with these H3K9 methyltransferases and CBX7 could derepress target genes and thereby induce growth arrest of leukemic cells. We found that pharmacologic inhibition of CBX7 abolishes the interaction of CBX7 with EHMT1/2 and SETDB1 and subsequently reduces H3K9 methylation levels which reactivates target gene expression. Reversely, upon pharmacologic inhibition of H3K9 methyltransferases, CBX7 can take over gene repression. Finally, we found that combined inhibition of CBX7 and EHMT1/2 or SETDB1 had additive effects on reducing cell growth and inducing differentiation. However, we did not detect changes in epigenetic modifications, nor target gene derepression, after combination treatment. In contrast, CBX7 inhibitors alone did affect both Polycomb-associated H2Aub-mediated gene repression as well as H3K9 methyltransferase activity. Therefore, we suggest that CBX7 is a promising therapeutic target in leukemia, as its inhibition can reactivate Polycomb and H3K9 methyltransferase target gene expression.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"142 ","pages":"Article 104691"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754804","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

KLF4 enhances transplantation-induced hematopoiesis by inhibiting TLRs and noncanonical NFκB signaling at a steady state

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2025.104730

Chun Shik Park , Cory S. Bridges , Andrew H. Lewis , Taylor J. Chen , Saptarsi Shai , Wa Du , Monica Puppi , Barry Zorman , Sumazin Pavel , H. Daniel Lacorazza

{"title":"KLF4 enhances transplantation-induced hematopoiesis by inhibiting TLRs and noncanonical NFκB signaling at a steady state","authors":"Chun Shik Park , Cory S. Bridges , Andrew H. Lewis , Taylor J. Chen , Saptarsi Shai , Wa Du , Monica Puppi , Barry Zorman , Sumazin Pavel , H. Daniel Lacorazza","doi":"10.1016/j.exphem.2025.104730","DOIUrl":"10.1016/j.exphem.2025.104730","url":null,"abstract":"<div><div>The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the <em>Klf4</em> gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and multilineage reconstitution, except for monocytes and T cells. However, the loss of KLF4 hindered hematologic reconstitution in competitive serial bone marrow transplants, highlighting a critical role for KLF4 in stress-induced hematopoiesis. Transcriptome analysis revealed an upregulation of NFκB2 and toll-like receptors (e.g., TLR4) in Klf4-null HSCs during homeostasis. Flow cytometry and immunoblot analysis confirmed the increased cell surface expression of TLR4 and the activation of NFκB2 in HSCs under homeostatic conditions, whereas NF<em>κ</em>B2 expression drops after radiation compared with steady-state levels. Our findings suggest that the constitutive activation of the TLR4–NFκB2 pathway inhibits the ability of HSCs to regenerate blood after transplantation in cytoablated bone marrow.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"144 ","pages":"Article 104730"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122536","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

Nucleic acid metabolism: the key therapeutic target for myeloid tumors 核酸代谢：髓系肿瘤的关键治疗靶点。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104693

Tomohiro Yabushita , Susumu Goyama

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The developmental clock: where art and science meet 发育时钟：艺术与科学交汇的地方。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104695

John D. Crispino

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Sex-stratified association of variants in the serotonin 1A receptor gene with acute crisis pain among African American patients with sickle cell disease 5 -羟色胺1A受体基因变异与非裔美国人镰状细胞病患者急性危重性疼痛的性别分层关联

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104692

Nilanjana Sadhu , Ying He , Yavnika Kashyap , Giokdjen Ilktach , Michael A. Wang , Yingwei Yao , Diana J. Wilkie , Robert E. Molokie , Zaijie Jim Wang

{"title":"Sex-stratified association of variants in the serotonin 1A receptor gene with acute crisis pain among African American patients with sickle cell disease","authors":"Nilanjana Sadhu , Ying He , Yavnika Kashyap , Giokdjen Ilktach , Michael A. Wang , Yingwei Yao , Diana J. Wilkie , Robert E. Molokie , Zaijie Jim Wang","doi":"10.1016/j.exphem.2024.104692","DOIUrl":"10.1016/j.exphem.2024.104692","url":null,"abstract":"<div><div>Patients with sickle cell disease (SCD) experience pain in their daily lives. Both the acute and chronic pain phenotypes of this disease exhibit high variability, making pain management a challenge. The underlying reasons for the phenotypic variability are poorly understood. Given the importance of serotonergic neurotransmission in pain signaling, we aimed to explore the role of variants in the 5-HT1A receptor gene (<em>HTR1A</em>) on pain variability in SCD. Four variants (rs6449693, rs878567, rs6294, and rs10042486) in <em>HTR1A</em> were genotyped in a cohort of 131 African Americans with SCD. Acute and chronic pain were measured by the acute care utilization and the McGill Pain Questionnaire, respectively. Association analyses were performed for three genetic models (additive, dominant, and recessive). Three variants (rs6449693, rs6294, and rs10042486) in <em>HTR1A</em> showed significant association with crisis pain in both the additive and dominant models. Although the G allele of rs6449693 and the C allele of rs10042486 associated with lower acute crisis pain, the T allele of rs6294 associated with increased acute crisis pain. Sex-stratified analyses revealed that the associations of these three variants with acute pain were significant only in men, but not in women. Furthermore, the A allele rs878567 that did not reach statistical significance in the overall cohort showed a significant association with lower crisis pain in men. To our knowledge, as the first study to explore the role of <em>HTR1A</em> variants in sickle cell pain, we identified that four variants across the gene are associated with acute crisis pain in SCD in a sex-stratified manner.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"142 ","pages":"Article 104692"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767462","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

Novel techniques to quantitatively assess age-dependent alterations in biophysical properties of HSPCs and bone marrow niche 定量评估HSPCs和骨髓生态位生物物理特性随年龄变化的新技术。

IF 2.5 4区医学

Experimental hematology Pub Date : 2025-02-01 DOI: 10.1016/j.exphem.2024.104686

Anthony D. Ho , Motomu Tanaka

{"title":"Novel techniques to quantitatively assess age-dependent alterations in biophysical properties of HSPCs and bone marrow niche","authors":"Anthony D. Ho , Motomu Tanaka","doi":"10.1016/j.exphem.2024.104686","DOIUrl":"10.1016/j.exphem.2024.104686","url":null,"abstract":"<div><div>The present knowledge on hematopoietic stem and progenitor cell (HSPC) biology and aging is based largely on studies in mouse models. Although mouse models are invaluable, they are not without limitations for defining how physical properties of HSPCs and their niche change with age. The bone marrow (BM) niche is a complex, interactive environment with multiple cell types. The structure and organization of the BM niche, especially the extracellular matrix (ECM), change with age. Provided with recent advances in quantitative analytical techniques and in vitro niche models, we have developed novel tools to quantitatively assess the impact of specific biochemical and physical cues on homing, adhesion, and migration of HSPCs. Recent developments in in vitro niche models have also provided new insights into the interactions between HSPCs and their niche, particularly the role of matrix stiffness. Further research is needed to integrate physical biomarkers into comprehensive mathematical models of age-dependent HSPC-niche interactions. The key is to use mouse models in conjunction with direct analyses in in vitro niche models to achieve a more comprehensive understanding of age-dependent alterations in niche function and regulation.</div></div>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"142 ","pages":"Article 104686"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754825","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