Alexandra Dreyzin, Noa G Holtzman, Challice L Bonifant
{"title":"CD123-targeting immunotherapeutic approaches in acute myeloid leukaemia.","authors":"Alexandra Dreyzin, Noa G Holtzman, Challice L Bonifant","doi":"10.1111/bjh.70019","DOIUrl":"https://doi.org/10.1111/bjh.70019","url":null,"abstract":"<p><p>Treatment of relapsed or refractory acute myeloid leukaemia (AML) has remained a significant challenge, with limited available targeted immunotherapies. CD123, or the interleukin-3 (IL-3) receptor, has long been known as a potential target expressed on AML blasts, and a range of different approaches to targeting CD123 have been trialled with variable anti-tumour responses and toxicities observed. Here, we review the clinical outcomes of these therapies, including monoclonal antibodies and antibody-drug conjugates, as well as bispecific T-cell engager molecules and chimeric antigen receptor (CAR) T cells. We discuss the potential reasons for therapy-associated toxicity and limited efficacy, including differential antigen expression, the AML microenvironment and patient-derived T-cell fitness. To address these challenges, we highlight novel approaches to CD123 targeting currently in preclinical development. Promising new strategies include combination therapies that target CD123 and other known AML-associated antigens such as CD33 or CLL-1, NK-cell-based cell therapies, and bispecific-secreting T cells.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705874","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":"Correction to 'Personalized therapy guided by single-cell transcriptomic analysis in relapsed and refractory KMT2A::MLLT10 AML with extensive extramedullary infiltration: A case report'.","authors":"","doi":"10.1111/bjh.70034","DOIUrl":"https://doi.org/10.1111/bjh.70034","url":null,"abstract":"","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697181","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}
Marie Hvelplund Kristiansen, Vibe Skov, Morten Kranker Larsen, Lasse Kjær, Hans Carl Hasselbalch, Troels Wienecke
{"title":"Prevalence and impact of additional CHIP mutations in JAK2V617F-positive ischaemic cerebrovascular patients.","authors":"Marie Hvelplund Kristiansen, Vibe Skov, Morten Kranker Larsen, Lasse Kjær, Hans Carl Hasselbalch, Troels Wienecke","doi":"10.1111/bjh.20242","DOIUrl":"https://doi.org/10.1111/bjh.20242","url":null,"abstract":"<p><p>The JAK2V617F mutation is associated with increased cardiovascular risk, including ischaemic stroke. This study investigates the prevalence of additional mutations in ischaemic cerebrovascular patients with and without JAK2V617F to better understand the mechanisms contributing to thrombotic risk. We examined 63 patients with the JAK2V617F mutation and 126 matched controls from a cohort of 591 ischaemic cerebrovascular patients. Somatic mutations were assessed using targeted next-generation sequencing (NGS). Serum thromboinflammatory markers were evaluated in a subset of patients. Additional somatic mutations were more common in JAK2V617F-positive patients than in controls (47.6% vs. 30.2%, p = 0.028). Patients with JAK2V617F had a higher prevalence of other mutations with variant allele frequencies (VAFs) above 10% (23.8% vs. 7.9%, p = 0.005), a pattern that persisted in cases with JAK2V617F <1% (p = 0.019). In JAK2V617F-positive patients, additional somatic mutations were associated with higher monocyte levels, even when excluding myeloproliferative neoplasms patients (p = 0.011). Patients with other clonal haematopoiesis of indeterminate potential mutations exhibited higher vascular cell adhesion molecule 1 (p = 0.027), soluble urokinase plasminogen activator receptor (p = 0.010) and IL-10 (p = 0.045), as well as higher neutrophil to lymphocyte ratio (p = 0.002). Ischaemic cerebrovascular patients with the JAK2V617F mutation more frequently harbour other somatic mutations and at higher VAF. This may reflect a more advanced clonal profile with relevance for vascular risk in JAK2V617F-positive individuals.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697182","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}
Angelica Barone, Chiara De Philippis, Federico Stella, Anna Dodero, Barbara Sarina, Martina Pennisi, Armando Santoro, Carmelo Carlo-Stella, Anna Guidetti, Stefania Bramanti, Paolo Corradini
{"title":"Allogeneic transplantation after failure of chimeric antigen receptor-T cells and exposure to bispecific antibodies: Feasibility, safety and survival outcomes.","authors":"Angelica Barone, Chiara De Philippis, Federico Stella, Anna Dodero, Barbara Sarina, Martina Pennisi, Armando Santoro, Carmelo Carlo-Stella, Anna Guidetti, Stefania Bramanti, Paolo Corradini","doi":"10.1111/bjh.70010","DOIUrl":"https://doi.org/10.1111/bjh.70010","url":null,"abstract":"<p><p>Clinical outcome after chimeric antigen receptor (CAR)-T-cell failure in large B-cell lymphoma (LBCL) is dismal. Allogeneic stem cell transplantation (alloSCT) represents a potentially curative salvage for relapsed/refractory LBCL, although concerns remain regarding its feasibility and safety in patients exposed to CAR-T and bispecific antibodies. Between 2019 and 2025, 83 disease progressions were documented among 170 LBCL patients treated with CAR-T in two academic centres; 69 (83%) started salvage treatment, the most frequent being glofitamab in 38 (55%); among those, we retrospectively analysed outcomes of 35 candidates for alloSCT consolidation. Ultimately, 13 (37%) underwent alloSCT after achieving complete (CR) or partial response. The median number of previous therapies was 5. All patients engrafted; grade III-IV acute graft-versus-host disease (GvHD) occurred in 8% and moderate-to-severe chronic GvHD in 15% of patients respectively. At 18.4-month median follow-up, non-relapse mortality was 0%; all allografted patients are alive in CR; conversely, the outcome of 22 patients not proceeding to transplant was poor, with a median overall survival of 11.7 months and 13 disease-related deaths (59%). Although in a small cohort of patients, our data highlight the potential benefit of alloSCT consolidation in selected responders to salvage regimens despite the extensive prior treatments with T-cell redirecting therapies.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688460","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}
Nasheed M Hossain, Kwang Woo Ahn, Jinalben Patel, Qinghua Lian, Bilal Abid, Ahmed Al Nughmush, Ulrike Bacher, Xia Bi, Shahrukh K Hashmi, Talal Hilal, Muhammad Husnain, Farhad Khimani, Richard T Maziarz, Dipenkumar Modi, Ron Ram, David Rizzieri, R Alejandro Sica, Amir Steinberg, Ravi Vij, Mazyar Shadman, Cameron Turtle, Mehdi Hamadani, Alex F Herrera
{"title":"Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS.","authors":"Nasheed M Hossain, Kwang Woo Ahn, Jinalben Patel, Qinghua Lian, Bilal Abid, Ahmed Al Nughmush, Ulrike Bacher, Xia Bi, Shahrukh K Hashmi, Talal Hilal, Muhammad Husnain, Farhad Khimani, Richard T Maziarz, Dipenkumar Modi, Ron Ram, David Rizzieri, R Alejandro Sica, Amir Steinberg, Ravi Vij, Mazyar Shadman, Cameron Turtle, Mehdi Hamadani, Alex F Herrera","doi":"10.1111/bjh.70020","DOIUrl":"https://doi.org/10.1111/bjh.70020","url":null,"abstract":"<p><p>CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a pivotal part of the treatment algorithm for large B-cell lymphoma (LBCL) in the second- and third-line settings based on numerous clinical trials. However, these studies included very few patients with a diagnosis of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS) and it is unclear if outcomes are similar to those observed with more common LBCL histologies. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we identified 111 HGBCL-NOS patients who received CAR-T therapy. The cytokine release syndrome (CRS) rate was 74% (7.7% grade 3+), median onset was 4 days (1-17) and immune effector cell-associated neurotoxicity syndrome rate was 45.2% (22.6% grade 3+), median onset was 7 days (1-17). At 2 years post-CAR-T infusion, the probability of overall survival and progression-free survival were 41.6% and 28.7% respectively. The 2-year non-relapse mortality and relapse/progression were 3.1% (95% confidence interval [CI]: 0.6-7.6) and 68.1% (95% CI: 57.9-77.6) respectively. Our analysis illustrates that patients with HGBCL-NOS represent a particularly difficult group to treat, even with CAR-T therapy. We observed that one third of patients achieved a durable response; however, the overall results were less favourable, with lower overall response rate, overall survival and progression-free survival as compared to published reports on LBCL.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688461","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}
Stephen P Hibbs, Jennifer Jones, Andrew Hantel, Lauren E Merz
{"title":"The Duffy antigen: A narrative review of testing, epidemiology, neutrophil counts and clinical consequences.","authors":"Stephen P Hibbs, Jennifer Jones, Andrew Hantel, Lauren E Merz","doi":"10.1111/bjh.20258","DOIUrl":"https://doi.org/10.1111/bjh.20258","url":null,"abstract":"<p><p>The null variant of the Duffy antigen is a non-pathological mutation that is partially protective against Plasmodium vivax and results in a lower absolute neutrophil count (ANC) in peripheral blood without increasing the risk of infection. Healthcare practices, clinical trials eligibility and medication dosing are often influenced by the definition of neutropenia. In many regions, however, neutropenia has been defined by the ANC distribution of Duffy-positive individuals, which may be unsuitable for decision-making in Duffy null individuals. This review describes the association between Duffy status, Plasmodium vivax exposure, racial or ethnic groupings and ANC. We outline biological and iatrogenic associations between Duffy antigen status and health outcomes and recommend changes to healthcare practices required to ensure equity for Duffy null individuals.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673417","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 impact of letermovir prophylaxis in matched sibling donor haematopoietic stem cell transplantation: Selecting the appropriate population for optimal prophylactic therapy.","authors":"Sisi Zhen, Li Liu, Futong Liu, Yuyan Shen, Tingting Zhang, Yuping Fan, Yuqing Cui, Ling Pan, Chen Liang, Yigeng Cao, Wenbin Cao, Jialin Wei, Weihua Zhai, Xin Chen, Qiaoling Ma, Rongli Zhang, Donglin Yang, Yi He, Aiming Pang, Mingzhe Han, Erlie Jiang, Sizhou Feng","doi":"10.1111/bjh.70016","DOIUrl":"https://doi.org/10.1111/bjh.70016","url":null,"abstract":"<p><p>Letermovir (LTV) effectively prevents cytomegalovirus (CMV) reactivation in CMV-seropositive patients. To evaluate the impact of LTV in matched sibling haematopoietic stem cell transplantation (HSCT) recipients, we retrospectively compared 72 matched sibling transplantation recipients receiving LTV with 134 controls. LTV significantly reduced 200-day CMV viraemia incidence (5.6% vs. 33.3%, p < 0.001). Multivariable analysis identified anti-thymocyte globulin (ATG) use (p = 0.005) and grade III-IV acute graft-versus-host disease (aGVHD; p < 0.001) as independent risk factors for CMV viraemia, while CMV serostatus did not significantly affect CMV viraemia (p = 0.448). Stratification based on risk factors (ATG, grade III-IV aGVHD) showed that LTV had a more significant effect on high-risk patients compared to low-risk patients. Also, LTV prophylaxis was associated with increased Epstein-Barr virus (EBV) viraemia (13.9% vs. 1.4%, p = 0.025) and higher CD20 monoclonal antibody utilization (11.1% vs. 1.4%, p = 0.046). Long-term survival remained similar between both groups. Results were validated in a second cohort from our centre. In conclusion, LTV prophylaxis significantly reduced CMV viraemia, especially in high-risk patients (ATG/grade III-IV aGVHD). However, the LTV group showed an elevated risk of EBV-related complications. Risk stratification-rather than CMV serostatus alone-should guide CMV prevention strategies in matched sibling HSCT. Larger clinical studies are needed for validation.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681699","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}
Rikke Hedegaard Jensen, Christian Teglgaard, Jonas Faartoft Jensen, Joachim Baech, Claus Werenberg Marcher, Anne Stidsholt Roug, Andreas Due Ørskov, Claudia Schöllkopf, Daniel Tuyet Kristensen, Rasmus Froberg Brøndum, Marianne Tang Severinsen
{"title":"Cardiotoxicity in patients with acute myeloid leukaemia following anthracycline-containing chemotherapy: A population-based matched cohort study.","authors":"Rikke Hedegaard Jensen, Christian Teglgaard, Jonas Faartoft Jensen, Joachim Baech, Claus Werenberg Marcher, Anne Stidsholt Roug, Andreas Due Ørskov, Claudia Schöllkopf, Daniel Tuyet Kristensen, Rasmus Froberg Brøndum, Marianne Tang Severinsen","doi":"10.1111/bjh.70026","DOIUrl":"https://doi.org/10.1111/bjh.70026","url":null,"abstract":"<p><p>Anthracycline-containing chemotherapy is associated with cardiovascular diseases (CVDs). While knowledge regarding the extent of cardiotoxicity in adult patients with acute myeloid leukaemia (AML) is sparse, anthracyclines remain a key component in the treatment. To address this, 1379 adult AML patients treated with anthracycline-containing chemotherapy between 2000 and 2020 were matched to 6895 comparators from the Danish background population and followed for a median of 11.8 and 12.8 years respectively. The risk of congestive heart failure (CHF) was higher in AML patients compared to the comparators throughout the entire follow-up period with adjusted hazard ratios (HRs) ranging from 15.0 (95% CI: 7.02-32.1) after 3 months to 2.68 (95% CI: 1.67-4.30) after 15 years. The risk of non-CHF CVD was initially higher in AML patients (adjusted HR: 9.16 [95% CI: 6.61-12.7] after 3 months) but converged to that of the comparators after approximately 10 years. Among AML patients, increasing age and male sex were identified as risk factors of CHF and non-CHF CVD. In summary, AML patients treated with anthracycline-containing chemotherapy had an elevated risk of CVD, particularly during the first years after treatment initiation. Increased focus on early detection and cardioprotective strategies may help mitigate the harmful effects of anthracyclines in the future.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681697","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}
Riccardo Masetti, Davide Leardini, Francesca Gottardi, Francesco Baccelli, Giorgio Antonio Maria Ottaviano, Francesca Vendemini, Francesco Saglio, Filomena Pierri, Mattia Algeri, Francesca Del Bufalo, Pietro Merli, Arcangelo Prete, Simone Cesaro, Marek Ussowicz, Maura Faraci, Marco Zecca, Franca Fagioli, Adriana Balduzzi, Jean-Hugues Dalle, Franco Locatelli, Daria Pagliara
{"title":"Outcomes of children with haematological malignancies given second haploidentical haematopoietic stem cell transplantation with either TCRαβ/CD19 depletion or post-transplant cyclophosphamide.","authors":"Riccardo Masetti, Davide Leardini, Francesca Gottardi, Francesco Baccelli, Giorgio Antonio Maria Ottaviano, Francesca Vendemini, Francesco Saglio, Filomena Pierri, Mattia Algeri, Francesca Del Bufalo, Pietro Merli, Arcangelo Prete, Simone Cesaro, Marek Ussowicz, Maura Faraci, Marco Zecca, Franca Fagioli, Adriana Balduzzi, Jean-Hugues Dalle, Franco Locatelli, Daria Pagliara","doi":"10.1111/bjh.70004","DOIUrl":"https://doi.org/10.1111/bjh.70004","url":null,"abstract":"<p><p>Human leukocyte antigen (HLA)-haploidentical haematopoietic cell transplantation (haplo-HCT) is a suitable salvage strategy in children with haematological malignancies experiencing either relapse or graft failure (GF) after the first HCT. Data comparing outcomes of transplant strategies using either TCRαβ/CD19 depletion (TCRαβ) or post-transplant cyclophosphamide (PTCy) are currently lacking. This retrospective, multicentre study included children with haematological malignancies who received a second haplo-HCT, in which either TCRαβ depletion or PTCy was used as the graft-versus-host disease (GvHD) prophylaxis strategy. Primary outcomes included overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). Overall, 123 patients were analysed, 56 receiving PTCy and 67 receiving TCRαβ. Median age at transplant was 9.1 years (range, 1.0-24.7 years). Relapse and GF were the transplant indications in 96 and 27 patients respectively. The 24-month OS [56.8% (95% CI: 42.5%-71.1%) vs. 43.2% (95% CI: 31.4%-55.1%)] and EFS [44.1% (95% CI: 30.3%-57.8%) vs. 35.8% (95% CI: 24.3%-47.3%)] did not differ between PTCy or TCRαβ cohorts. The CIR [34.0% (95% CI: 23.1%-50.1%) vs. 37.3% (95% CI: 27.3%-50.8%), p = 0.28] and NRM [18.9% (95% CI: 10.7%-33.4%) vs. 25.3% (95% CI: 16.8%-38.2%), p = 0.48] were comparable. Cumulative incidence of 100-day of any-grade acute GvHD was higher in the PTCy cohort [55.3% (95% CI: 43.7%-70.4%) vs. 32.8% (95% CI: 23.3%-46.2%), p = 0.02], with non-statistically significant differences for grade II-IV and grade III-IV. The 24-month cumulative incidence of chronic GvHD was higher in the PTCy cohort [38.8% (95% CI: 27.6%-54.6%) vs. 11.9% (95% CI: 6.2%-22.8%), p < 0.01], including moderate-severe forms [15.3% (95% CI: 8.1%-29.1%) vs. 1.4% (95% CI: 0.2%-10.4%), p < 0.01]. Infectious complications were comparable except for a higher adenovirus reactivation rate in the TCRαβ group (14.3% vs. 29.9%, p = 0.04). PTCy and TCRαβ offer comparable clinical outcomes in the setting of second haplo-HCT, although PTCy is associated with a higher incidence of GvHD and lower adenovirus reactivation.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681698","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}
Xingyue Li, Qi Zhou, Xiaowen Hao, Can Cao, Seyram Yao Adzraku, Xuguang Song, Cai Sun, Xiaofeng Guo, Yue Li, Shengnan Yuan, Yujin Huang, Kailin Xu, Jianlin Qiao, Lingyu Zeng, Wen Ju
{"title":"Targeting NLRP1-CCL8 axis in the leukaemic niche suppresses AML via inhibition of PI3K-AKT signalling.","authors":"Xingyue Li, Qi Zhou, Xiaowen Hao, Can Cao, Seyram Yao Adzraku, Xuguang Song, Cai Sun, Xiaofeng Guo, Yue Li, Shengnan Yuan, Yujin Huang, Kailin Xu, Jianlin Qiao, Lingyu Zeng, Wen Ju","doi":"10.1111/bjh.70011","DOIUrl":"https://doi.org/10.1111/bjh.70011","url":null,"abstract":"<p><p>Bone marrow microenvironment not only plays a key role in supporting normal haematopoiesis but also plays an important role in regulating the progression of acute myelogenous leukaemia (AML). Targeting the bone marrow microenvironment will provide new targets for AML treatment. However, until now, the mechanism by which the bone marrow microenvironment promotes AML progression remains obscure. Our previous studies have found that the bone marrow microenvironment Nucleotide-binding Oligomerization Domain (NOD)-Leucine Rich Repeat (LRR)-containing Receptors (NLR) family pyrin domain containing 1 (NLRP1) plays an important role in the regulation of bone marrow endothelial cells, mesenchymal stem cell (MSC) cells and haematopoiesis, but the effect of the bone marrow microenvironment NLRP1 on AML has not been addressed. In this study, we found that niche Nlrp1 KO inhibited AML disease progression and leukaemia stem cell activity. Moreover, Nlrp1 was expressed in the bone marrow microenvironment, especially in MSC. Nlrp1 knockout in MSC inhibits the growth and proliferation of co-cultured leukaemia cells, which is related to Nlrp1 KO inhibition of Ccl8 secretion in MSC and CCL8/CCR1-mediated PI3K-AKT activation in AML cells. Our study highlights the critical role of niche NLRP1 in AML and it could be a therapeutic target for AML.</p>","PeriodicalId":135,"journal":{"name":"British Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673416","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}