Lu Lu, Chenfei Liu, Lezong Chen, Xumiao Zhang, Yinglin Su, Zhenzhen Chou, Yang Liang, Yuanbin Song
{"title":"Understanding erythroid physiology and pathology in humanized mice: A closer look.","authors":"Lu Lu, Chenfei Liu, Lezong Chen, Xumiao Zhang, Yinglin Su, Zhenzhen Chou, Yang Liang, Yuanbin Song","doi":"10.1111/bjh.20023","DOIUrl":"https://doi.org/10.1111/bjh.20023","url":null,"abstract":"<p><p>Erythropoiesis, the process of red blood cell (RBC) development from haematopoietic stem cells, is crucial in haematology research due to its intricate regulation and implications in various pathologies such as anaemia and haemoglobinopathies. Humanized mice, created by introducing human cells or tissues into immunodeficient mice, offer a promising avenue in vivo approach. However, challenges persist in fully replicating human erythropoiesis in these models, particularly in generating mature human RBCs capable of sustained circulation. This review discusses the differences between human and mouse erythropoiesis, recent progress made using refined humanized mouse models for studying human erythropoiesis and erythropoietic disorders, the challenges that impede a faithful mimicking of human phenotypes in these mice and recommendations for future research improvements. Despite progress being made, enhancing the translational potential of humanized mouse models for human erythropoiesis research remains a priority.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute myeloid leukaemia with SRSF2 and BRAF mutations preceded by histiocytic proliferation in the bone marrow.","authors":"Minako Mori, Tomomi Sakai, Tomomi Oka, Maki Sakurada, Makoto Iwasaki, June Takeda, Junya Kanda, Yasuhito Nannya, Seishi Ogawa, Akifumi Takaori-Kondo, Koki Moriyoshi, Hiroshi Kawabata","doi":"10.1111/bjh.20028","DOIUrl":"https://doi.org/10.1111/bjh.20028","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Outcomes and prognostic factors associated with relapse after haploidentical stem cell transplantation for paediatric T-cell acute lymphoblastic leukaemia.","authors":"Chen Zhao, Meng-Yu Xiao, Feng Zhang, Lu Bai, Guan-Hua Hu, Pan Suo, Feng-Rong Wang, Zhi-Dong Wang, Xiao-Dong Mo, Yu Wang, Yuan-Yuan Zhang, Lan-Ping Xu, Xiao-Jun Huang, Yi-Fei Cheng, Xiao-Hui Zhang","doi":"10.1111/bjh.20007","DOIUrl":"https://doi.org/10.1111/bjh.20007","url":null,"abstract":"<p><p>The outcomes are poor for paediatric patients with T-cell acute lymphoblastic leukaemia (T-ALL) who relapse after haematopoietic stem cell transplantation (HSCT). However, studies focusing on paediatric patients with T-ALL following haploidentical HSCT (haplo-HSCT) are limited. We retrospectively identified a consecutive cohort comprising of 128 paediatric T-ALL after haplo-HSCT from 2642 consecutive ALL patients between January 2010 and June 2022. The 2-year overall survival and leukaemia-free survival were 67.77% ± 4.21% and 66.34% ± 3.82%, respectively, and the cumulative incidence of relapse (CIR) and non-relapse mortality were 33.82% ± 0.70% and 12.65% ± 0.46% respectively. According to the multivariate Cox regression analysis, CD34 cells, minimal residual disease (MRD) ≥0.01% before HSCT, chronic graft-versus-host disease (cGvHD) and cytomegalovirus were associated with relapse (p < 0.05). To develop a scoring system for stratifying patients, we combined the variables and stratified them into low (0-2 points) and high (3, 4) groups. Consequently, the 2-year CIR in low and high groups were 23.76% ± 1.83% and 48.22% ± 2.42% (p = 0.009), respectively. Children with T-ALL have poor long-term survival, and haplo-HSCT is a potent and safe treatment; however, the incidence of relapse is high. Eliminating pre-HSCT MRD, guaranteeing sufficient CD34 cells infusion and the occurrence of cGvHD and cytomegalovirus reactivation may benefit from relapse.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianyu Sun, Shalini Singh, Hayson Chenyu Wang, Juseong Lee, Hamid Dolatshad, Pak Leng Cheong, Douglas R Higgs, Jacqueline Boultwood, Andrea Pellagatti
{"title":"Identification of new candidate drugs in myelodysplastic syndromes with splicing factor mutations by transcriptional profiling and connectivity map analysis.","authors":"Tianyu Sun, Shalini Singh, Hayson Chenyu Wang, Juseong Lee, Hamid Dolatshad, Pak Leng Cheong, Douglas R Higgs, Jacqueline Boultwood, Andrea Pellagatti","doi":"10.1111/bjh.20026","DOIUrl":"https://doi.org/10.1111/bjh.20026","url":null,"abstract":"<p><p>We sought to identify new candidate drugs for repurposing to myelodysplastic syndromes (MDS). Connectivity map analysis was performed on gene expression signatures generated from bone marrow CD34<sup>+</sup> cells of splicing factor mutant MDS patients. Celastrol and Withaferin A (WA), two top-ranking compounds identified, markedly inhibited proliferation, arrested the cell cycle and induced apoptosis in leukaemia cells. These compounds also inhibited the viability of primary bone marrow MDS cells. We showed that Celastrol and WA inhibit interleukin-1 receptor-associated kinase 4-mediated nuclear factor kappa-light-chain-enhancer of activated B cells signalling activation in splicing factor mutant MDS and leukaemia cells. Celastrol and WA may represent novel candidate drugs for the treatment of MDS.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How I treat iron-refractory iron deficiency anaemia-An expert opinion-based treatment guidance for children and adults.","authors":"V Hoving, A E Donker, S E M Schols, D W Swinkels","doi":"10.1111/bjh.20030","DOIUrl":"https://doi.org/10.1111/bjh.20030","url":null,"abstract":"<p><p>Iron-refractory iron deficiency anaemia (IRIDA) is a rare hereditary microcytic anaemia characterized by partial or complete resistance to oral iron supplementation, caused by elevated plasma hepcidin levels resulting from pathogenic variants in the TMPRSS6 gene. Although intravenous iron supplementation is often effective, patient responses can vary significantly due to various factors, and potential side effects of this treatment remain unclear. Additionally, evidence-based international guidelines for diagnosing and managing IRIDA are lacking. This review aims to provide patient-tailored treatment strategies, informed by case studies and expert opinion, to address the specific therapeutic needs of both children and adults with IRIDA.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisabetta Metafuni, Filippo Achille Brioschi, Andrea Patriarca, Claudia Leoni, Giorgia Battipaglia, Daniela Carlino, Annalisa Condorelli, Valeria Di Giacomo, Sarah Marktel, Maria Antonietta Marzilli, Maurizio Miglino, Esther Natalie Oliva, Antonella Sau, Alessandra Ricco, Grazia Sanpaolo, Annarita Trolese, Anna Paola Iori, Simona Sica, Wilma Barcellini, Bruno Fattizzo
{"title":"Real-world evidence of pegcetacoplan in patients with paroxysmal nocturnal haemoglobinuria: A nationwide Italian study.","authors":"Elisabetta Metafuni, Filippo Achille Brioschi, Andrea Patriarca, Claudia Leoni, Giorgia Battipaglia, Daniela Carlino, Annalisa Condorelli, Valeria Di Giacomo, Sarah Marktel, Maria Antonietta Marzilli, Maurizio Miglino, Esther Natalie Oliva, Antonella Sau, Alessandra Ricco, Grazia Sanpaolo, Annarita Trolese, Anna Paola Iori, Simona Sica, Wilma Barcellini, Bruno Fattizzo","doi":"10.1111/bjh.20025","DOIUrl":"https://doi.org/10.1111/bjh.20025","url":null,"abstract":"<p><p>In this study, we collected real-world evidence on the use of pegcetacoplan among 22 Italian patients with paroxysmal nocturnal haemoglobinuria showing suboptimal response to anti-C5 treatments eculizumab and ravulizumab. Most patients exhibited a complete or good response as per the criteria of the European Bone Marrow Transplant group (Risitano et al. Front Immunol 2019) and median haemoglobin improvement from baseline was +3.6 g/dL. During the 6-month follow-up, 27% of patients displayed a breakthrough haemolytic event mainly managed with supportive treatment. No thromboses occurred.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick Connerty, Jinhan Xie, Fatima El-Najjar, Toby N Trahair, Nisitha Jayatilleke, Chelsea Mayoh, Richard B Lock
{"title":"Immune-deficient MISTRG mice support expansion of leukaemia-initiating cells in xenograft models of paediatric acute myeloid leukaemia.","authors":"Patrick Connerty, Jinhan Xie, Fatima El-Najjar, Toby N Trahair, Nisitha Jayatilleke, Chelsea Mayoh, Richard B Lock","doi":"10.1111/bjh.20029","DOIUrl":"https://doi.org/10.1111/bjh.20029","url":null,"abstract":"<p><p>Acute myeloid leukaemia (AML) remains a deadly disease, largely due to the persistence of drug-resistant leukaemia-initiating cells (LICs) which promote relapse. Therefore, effective therapies must target LICs. Patient-derived xenografts (PDXs) are valuable for testing new therapies, though establishing AML PDX models is challenging. Two humanized mouse strains, MISTRG and NRGS, have been developed for this purpose. In this study, we show both are suitable strains for the development of AML PDXs; however, MISTRG-derived PDXs contain 10 times higher LIC frequencies than NRGS-derived PDXs. These differences have crucial implications for preclinical AML therapy testing and modelling relapse models of the disease.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maternal and perinatal outcomes of sickle cell disease in pregnancy: A nationwide study in France.","authors":"Alice Corsia, Laure Joseph, Nathanael Beeker, Sandra Manceau, Marine Driessen, Benoit Meunier, Marina Cavazzana, Mathis Collier, Jean-Marc Treluyer","doi":"10.1111/bjh.20009","DOIUrl":"https://doi.org/10.1111/bjh.20009","url":null,"abstract":"<p><p>This nationwide cohort study provides a comprehensive overview of maternal and perinatal outcomes associated with sickle cell disease (SCD) during pregnancy. Using the French national health database, all singleton pregnancy-related hospital discharges from 2013 to 2020 in women aged 15-55 (n = 5 752 080) were selected. Of these, 1022 births were to women with SCD, 308 of whom were on long-term treatment, that is, hydroxyurea (HU) and/or transfusion programme. Pregnancies with SCD were more likely to involve pre-eclampsia (9.6% vs. 1.7%; p < 0.001), pulmonary embolism (0.70% vs. 0.02%; p < 0.001), caesarean sections (52.8% vs. 18.2%; p < 0.001) and postpartum haemorrhage (8.3% vs. 4.1%; p < 0.001) compared to pregnancies without SCD. Preterm birth (<37 weeks) was much more common in women with SCD (28.5% vs. 5.6%). Infants born to women with SCD faced greater adverse neonatal outcomes (22.4% vs. 8.0%; p < 0.001). Although untreated SCD was linked to fewer complications than long-term treated SCD, both conditions presented greater risks compared with pregnancies without SCD. Unexpectedly, babies born to women with SCD had a higher incidence of congenital abnormalities (6.3% vs. 3.4%; p < 0.001), not attributed to HU use. Overall, despite advances in SCD management, pregnancy in SCD remains a high-risk condition, for both mothers and babies.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jahanzaib Khwaja, Sriram Ravichandran, Oliver Cohen, Darren Foard, May Low, Ana Martinez-Naharro, Lucia Venneri, Marianna Fontana, Philip N Hawkins, Julian Gillmore, Helen J Lachmann, Carol Whelan, Shameem Mahmood, Ashutosh Wechalekar
{"title":"Outcomes of daratumumab-bortezomib-thalidomide-dexamethasone in treatment-naive systemic AL amyloidosis.","authors":"Jahanzaib Khwaja, Sriram Ravichandran, Oliver Cohen, Darren Foard, May Low, Ana Martinez-Naharro, Lucia Venneri, Marianna Fontana, Philip N Hawkins, Julian Gillmore, Helen J Lachmann, Carol Whelan, Shameem Mahmood, Ashutosh Wechalekar","doi":"10.1111/bjh.20021","DOIUrl":"https://doi.org/10.1111/bjh.20021","url":null,"abstract":"<p><p>Systemic light chain (AL) amyloidosis is an incurable disorder caused by extra-cellular deposition of light-chain aggregates in critical organs. An immunomodulatory agent-based quadruplet including anti-CD38 therapy has not been investigated as a first-line treatment in AL amyloidosis. We report the UK experience of daratumumab-bortezomib-thalidomide-dexamethasone for the first-line treatment of AL amyloidosis. Consecutive patients with a new diagnosis of systemic AL between 2021 and 2023 were retrospectively reviewed from the UK National Amyloidosis Centre database. One hundred and two patients were included; median age was 61 years, involved free light-chain concentration 234 mg/L, 65% had cardiac and 63% renal involvement with modified Mayo stage I/II/IIIa/IIIb in 24%/36%/21% and 19% respectively. A median of 6 cycles was delivered. By intention-to-treat analysis, best haematological overall response rate was 97%: complete response at 65%, very good partial response at 22%, partial response at 11% and no response at 3%. At 6- and 12-month time points from treatment initiation, best cardiac response rates were 39% and 45%, respectively, for evaluable patients. At a median duration of 18 months follow-up, the estimated 1-year overall survival was 89% (95% confidence interval [CI] 81-94) and treatment-free survival/death was 82% (95% CI 73-89). We demonstrate efficacy in this real-world population with comparable results to the gold standard, daratumumab-bortezomib-cyclophosphamide-dexamethasone.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The potential role of the αVβ3 integrin receptor in placental biology and normal and complicated pregnancies.","authors":"Amihai Rottenstreich, Barry S Coller","doi":"10.1111/bjh.20019","DOIUrl":"10.1111/bjh.20019","url":null,"abstract":"<p><p>The αVβ3 receptor is a member of the integrin family of receptors, which includes 24 members involved in a variety of key biological processes. It is widely expressed in multiple cell types and is involved in cell adhesion and migration, angiogenesis and immune cell regulation. These processes play important roles in both normal placentation and placental progression through pregnancy. This review describes the potential roles of αVβ3 integrin receptor throughout gestation in normal and abnormal conditions, and the need for additional studies to better define its precise contributions.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}