Experimental hematology最新文献

{"title":"Mast Cell Derived Histamine Negatively Regulates Hematopoiesis.","authors":"Bailey R Klein, Julianne N P Smith, Ramachandra Katabathula, Ritisha Rashmil, Sofia X Wilhelm, Rahul Chaudhary, Karina Inacio Ladislau De Carvalho, Zhenxiang Gao, Brittany A Cordova, Eric E Irons, Benjamin Kovacic, Shikha Parsai, Vladimir Makarov, Frederick Petroze, Riya Tiwari, Stanton L Gerson, Rong Xu, Sanford D Markowitz, Amar B Desai","doi":"10.1016/j.exphem.2026.105893","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105893","url":null,"abstract":"<p><p>Mast cells (MCs) are well known for their roles in immunity, but their influence on hematopoietic stem cell (HSC) regulation remains poorly defined. Here, we identify MC-derived histamine as a suppressor of hematopoiesis. MC-deficient \"SASH\" mice exhibited increased bone marrow HSC frequency, a transcriptional quiescence signature, and resistance to myeloablative chemotherapy, associated with niche remodeling, including increased HSC-supportive stromal populations and elevated maintenance factor expression, and improved engraftment of wild-type donor cells. Reciprocal transplants showed this phenotype is driven by the recipient niche rather than an HSC-intrinsic property, and MC-derived secretory factors were directly sufficient to suppress HSCs in vitro and in vivo. Pharmacologic H1 receptor blockade with cetirizine, an FDA-approved inverse agonist, phenocopied the SASH model, expanding HSCs and enhancing both early recovery and long-term reconstitution in transplant settings, while exogenous histamine reversed the SASH phenotype. Supporting clinical relevance, electronic health record analysis revealed that antihistamine use was associated with elevated white blood cell counts in humans. These findings establish mast cell-derived histamine as a suppressor of hematopoiesis and suggest that H1R antagonism may offer a tractable strategy to enhance hematopoietic regeneration. Teaser Abstract: Mast cell-derived histamine restrains hematopoietic stem cell activity by shaping the bone marrow niche. Blocking histamine signaling with the FDA-approved antihistamine cetirizine expands the stem and progenitor pool and accelerates hematopoietic recovery after transplant, pointing to a repurposable strategy for boosting blood regeneration in patients.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105893"},"PeriodicalIF":2.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886874","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}

{"title":"Share your research in Experimental Hematology—Announcing exciting new article types!","authors":"","doi":"10.1016/j.exphem.2026.105492","DOIUrl":"10.1016/j.exphem.2026.105492","url":null,"abstract":"","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":"161 ","pages":"Article 105492"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725466","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}

{"title":"Phenotypic Remodeling and Functional Impairment of Circulating Neutrophils Are Associated with Infection-Related Mortality in Acute Myeloid Leukemia.","authors":"Alexandra Fernandes Callera, Camila Peloso Ferreira, Daiane Franciele Rech, Evandro Secchi Rosa, Felipe Anastácio Da Silva Machado, Heloisa Adriana Gomes De Pinho, Silvania Pereira Lanes, Vanessa Renó Mattos, Fernando Callera","doi":"10.1016/j.exphem.2026.105872","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105872","url":null,"abstract":"<p><p>Infectious complications remain a leading cause of early mortality in patients with acute myeloid leukemia (AML), yet the contribution of qualitative neutrophil abnormalities to infectious risk remains poorly understood. We prospectively evaluated circulating neutrophil phenotypes and oxidative burst reserve in 27 consecutive patients with newly diagnosed AML treated at two tertiary referral centers. Neutrophil subsets were characterized by multiparameter flow cytometry according to CD16/CD62L expression and compared with those of healthy controls (n = 10) and AML patients in complete remission after induction therapy (n = 10). At diagnosis, patients exhibited expansion of activated-like N1 and immature N2B subsets, contraction of the predominant homeostatic N2A population, and impaired oxidative burst reserve (all p < 0.05). Both phenotypic abnormalities and oxidative burst partially recovered after induction therapy. Infection-related mortality occurred in 22.2% of patients. After adjustment for age, the log-transformed N1/N2A ratio remained independently associated with infection-related mortality (adjusted OR 4.90, 95% CI 1.17-20.49; p = 0.029). The ratio also demonstrated moderate discriminatory performance (AUC 0.774, 95% CI 0.585-0.963; p = 0.049), and the optimal cutoff (-2.022) identified patients with significantly inferior infection-related survival (HR 12.83, 95% CI 2.62-62.90; log-rank p = 0.0017). In addition, higher log(N1/N2A) values were associated with lower oxidative burst reserve (Spearman r = -0.45; p = 0.018). These findings suggest that neutrophil phenotypic remodeling reflects innate immune dysfunction in AML and that the log-transformed N1/N2A ratio may serve as a practical biomarker for early identification of patients at increased risk of infection-related mortality.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105872"},"PeriodicalIF":2.7,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857149","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}

{"title":"Evolution in the cryopreservation of hematopoietic stem cells.","authors":"Krishna Patel, Victoria E Siltamäki, Robert N Ben, Nicolas Pineault","doi":"10.1016/j.exphem.2026.105873","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105873","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) are essential for the reconstitution of the hematopoietic and immune systems and are widely used in transplantation and emerging cell-based therapies. Cryopreservation is a critical technology enabling long-term storage, banking, and distribution of HSC grafts and immuno-oncology cell products. However, the cryopreservation process exposes stem cells and progenitors to multiple sources of cryoinjury, including intracellular ice formation, osmotic shock, solute effects and ice recrystallization, which can compromise post-thaw viability, recovery and functional potency. For decades, dimethyl sulfoxide (DMSO) has remained the gold-standard cryoprotective agent (CPA) due to its ability to reduce osmotic stress, limit intracellular ice formation and stabilize cellular structures. Despite its widespread use, it is associated with dose- and time-dependent cytotoxicity and adverse infusion-related reactions, motivating efforts to reduce or replace its use. This review summarizes key cryobiological principles underlying HSC preservation, including the importance of optimized CPA exposure, controlled cooling, rapid thawing, and storage below glass transition temperature. We also discuss established and emerging permeating and non-permeating CPAs, including sugars, polymers, and carbohydrate-based ice recrystallization inhibitors (IRI), several of which have shown to improve post-thaw outcomes and engraftment in preclinical models. Finally, we review strategies to mitigate DMSO toxicity, including reduced-DMSO formulations and newly developed \"all-in-one\" DMSO-free cryosolutions. Collectively, these advances are driving the evolution of safer and more effective cryopreservation strategies for HSC transplantation and next-generation cellular therapeutics.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105873"},"PeriodicalIF":2.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839676","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}

{"title":"Prognostic model based on calcium-related genes predicts prognosis and reveals the immune landscape of acute myeloid leukemia.","authors":"Jing Duan, Hu Zhang, Junjie Chu, Xiangdong Duan","doi":"10.1016/j.exphem.2026.105870","DOIUrl":"https://doi.org/10.1016/j.exphem.2026.105870","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) exhibits heterogeneous outcomes and lacks reliable prognostic markers. As a critical regulator of cell fate, calcium signaling's prognostic value in AML requires investigation. This study aims to construct a calcium-related gene (CRG)-based prognostic model for AML. Differential analysis on RNA-seq data was conducted for AML from TCGA and GEO. Intersecting differentially expressed genes and CRGs yielded AML-associated differentially expressed CRGs (DECRGs). A prognostic model was developed through univariate/multivariate Cox regression and LASSO, and validated in a GEO dataset. Bioinformatics analyses explored the links between risk groups and immune characteristics, genomic mutations, and drug sensitivity. Key genes' effects on cell proliferation, apoptosis, and differentiation were verified in vitro using CCK-8 assay, colony formation assay, and flow cytometry. The 13-DECRG-based model distinguished high- and low-risk patients in both training and validation cohorts, with high-risk patients showing a worse prognosis. The risk score was an independent prognostic factor. Immune analysis revealed a unique immune microenvironment for the high-risk group. CAMK2A overexpression inhibited cell proliferation and colony-forming ability, promoted cell apoptosis, and induced an increased proportion of CD11b- and CD14-positive cells. In vitro experiments indicated CAMK2A-induced suppression of AML cells' malignant phenotype by activating the P53 signaling pathway. An AML CRG-based model with favorable risk stratification performance was constructed. In vitro experiments revealed CAMK2A-induced inhibition of the malignant phenotype via suppressing proliferation, promoting apoptosis, and facilitating myeloid differentiation in AML cells. This study provides novel evidence for understanding CRGs in AML as well as the potential functions of CAMK2A.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105870"},"PeriodicalIF":2.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817937","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}

{"title":"PCBP1 Joins the Regulatory Network of the Endothelial-to-Hematopoietic Transition.","authors":"Tomomasa Yokomizo","doi":"10.1016/j.exphem.2026.105494","DOIUrl":"10.1016/j.exphem.2026.105494","url":null,"abstract":"<p><p>Ji and colleagues show that endothelial deletion of PCBP1, a multifunctional nucleic acid-binding protein, reduces intra-arterial hematopoietic cluster formation, and impairs subsequent hematopoietic development. These findings identify PCBP1 as a new regulator of early definitive hematopoiesis although leaving its underlying molecular mechanism unresolved.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105494"},"PeriodicalIF":2.7,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764412","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}

{"title":"Unlocking the curative potential of gene transfer and editing for hematopoietic disorders.","authors":"Kohei Shiroshita, Anne Stolz, Camille Malouf, Vu L Tran, Jingjing Li, Mitchell J Weiss, Luigi Naldini","doi":"10.1016/j.exphem.2026.105493","DOIUrl":"10.1016/j.exphem.2026.105493","url":null,"abstract":"<p><p>Hematopoietic stem and progenitor cells (HSPCs) gene therapy may transform the therapeutic landscape for inherited hematological disorders and already offers potentially curative options for some diseases, including inborn errors of immunity and β-hemoglobinopathies. Its continued success relies on further refinement of gene transfer technologies, gene-editing tools such as clustered regularly interspaced short palindromic repeats (CRISPR) and associated systems (CRISPR-Cas), and optimized ex vivo HSPC manipulation protocols that ensure robust, long-term engraftment and clonal diversity with reduced-toxicity, nongenotoxic conditioning strategies. Here, we reviewed recent developments and refinements in gene transfer and editing technologies for HSPCs, while also discussing the critical limitations and hurdles to clinical translation, as recently presented at the New Investigator Committee Gene Therapy webinar. Future directions must prioritize integrating technological innovation with the development of equitable and simplified models to reduce costs and ensure that these life-saving cellular therapies reach patients worldwide.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105493"},"PeriodicalIF":2.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758608","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}

{"title":"Development of receptor and oncogene-responsive luciferase reporter vectors that are activated via kinase signaling to AP-1.","authors":"Daniel J L Coleman, Luke Ames, Hurooul Aain, Joanna Gamble, Kinga Koscielniak, Zijin Zhang, Cherisse Lau, Abigail Joyce, Peter N Cockerill","doi":"10.1016/j.exphem.2026.105491","DOIUrl":"10.1016/j.exphem.2026.105491","url":null,"abstract":"<p><p>This study aimed to generate lentiviral vectors carrying an array of AP-1 motifs driving luciferase gene expression as reporters of mitogen-activated protein kinase (MAPK) activity. We created a series of vectors based on LeGO-iG that were used to generate stably transduced leukemia cell lines. A vector termed LEGO-AP1×6-GM55 containing an array of 6 AP-1 sites linked to the minimal CSF2 promoter was sufficient to support high levels of MAPK-inducible luciferase activity in leukemic cell lines that was suppressed by MAPK inhibitors. The inclusion of a putative chromatin priming element encompassing RUNX and ETS motifs increased the activity of these vectors. The additional inclusion of the full-length mouse CSF2 promoter, or the human DUSP5 promoter further increased the MAPK-dependent activity of these vectors in leukemic cells. These vectors support moderate levels of constitutive activity in cells carrying mutations that activate the RAS/RAF/MEK MAPK signaling pathway, and high-level activity after direct activation of MAPK signaling. They also respond to T-cell receptor activation via MAPK and Ca2+ signaling pathways. This resource will now make it easier to track receptor or oncogene-inducible MAPK activity in cultured cells, and potentially in tumors, close to real-time.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105491"},"PeriodicalIF":2.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757837","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}

{"title":"Hematopoietic Stem Cell States, Function, and Molecular Identity: From Quantitative Assays to Modern Multiomics.","authors":"Tom Q T Bui, Franziska Mey, Ly P Vu, Karsan Aly","doi":"10.1016/j.exphem.2026.105489","DOIUrl":"10.1016/j.exphem.2026.105489","url":null,"abstract":"<p><p>Hematopoietic stem and progenitor cells (HSPCs) are characterized by the ability to proliferate, differentiate into multiple lineages, self-renew, and repopulate the hematopoietic system. Development of functional assays enabling qualitative and quantitative measurements of these different features are cornerstones of the field. In this review, we summarize key approaches from early transplantation and spleen colony-forming unit assays to in vitro clonogenic systems, long-term culture assays, xenotransplantation models, and single-cell platforms with historical perspectives and evaluation of their utilities as well as limitations. We emphasize the principles of functional definition of stem and progenitor cells and the discoveries of clonal origin and functional heterogeneity within phenotypically defined HSPC populations.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105489"},"PeriodicalIF":2.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688746","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}

{"title":"Peripheral Blood Profiles Reflecting Progenitor Lineage Balance are Associated With Molecular Response in Chronic Myeloid Leukemia.","authors":"Kohjin Suzuki, Naoki Watanabe, Yutaka Tsukune, Tadaaki Inano, Shintaro Kinoshita, Kazuhiro Yamada, Miki Ando, Tomoiku Takaku","doi":"10.1016/j.exphem.2026.105488","DOIUrl":"10.1016/j.exphem.2026.105488","url":null,"abstract":"<p><p>Early achievement of deep remission improves patients' outcome in chronic myeloid leukemia (CML) treatment, highlighting the need for predictive indicators before therapy initiation. This study aimed to investigate whether baseline hematologic profiles are associated with molecular response in CML. Using hierarchical clustering of complete blood count (CBC) data at diagnosis, patients were stratified into two clusters. Patients in Cluster 1 had higher BCR::ABL1^IS mRNA levels at 3 and 6 months post-treatment and lower rates of major molecular response compared with cluster 2. Cluster 1 also showed increased granulocyte and immature white blood cell counts and decreased erythroid parameters. Flow cytometric analysis of bone marrow mononuclear cells revealed that cluster 1 had a significant increase in hematopoietic stem cell fractions and a higher ratio of granulocyte-macrophage progenitors to megakaryocyte-erythroid progenitors compared with cluster 2. These findings suggest that differences in bone marrow progenitor cell differentiation affect peripheral blood profiles. Artificial intelligence-driven ghost cytometry (GC) comprehensively captured these differences, distinguishing poor responders, with diagnostic GC scores correlating with BCR::ABL1^IS mRNA levels. The study indicates that multivariate analysis of CBC and GC captures biological features associated with early molecular response in CML.</p>","PeriodicalId":12202,"journal":{"name":"Experimental hematology","volume":" ","pages":"105488"},"PeriodicalIF":2.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668809","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}