Haematologica最新文献_第6页

Metallothionein 1: the Achilles heel of Dnmt3a;Npm1-mutant acute myeloid leukemia. 金属硫蛋白1:Dnmt3a的致命弱点npm1突变型急性髓性白血病。

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-18 DOI: 10.3324/haematol.2025.288820

Bowen Yan,Olga A Guryanova

引用次数: 0

IGLV3-21^R110-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia. iglv3 - 21r110定向双特异性抗体激活T细胞并促进慢性淋巴细胞白血病高危亚群的杀伤。

IF 7.9 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.287697

Claudia Fischer, Shih-Shih Chen, Johanna Nimmerfroh, Anne Eugster, Simon Stücheli, Christoph Schultheiß, Corinne Widmer, Dominik Heim, Benjamin Kasenda, Jakob Passweg, Sebastian Kobold, Lukas Egli, Nicolò Coianiz, Obinna Chijioke, Nicholas Chiorazzi, Marie Follo, Heinz Läubli, Matthias Peipp, Mascha Binder

{"title":"IGLV3-21R110-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia.","authors":"Claudia Fischer, Shih-Shih Chen, Johanna Nimmerfroh, Anne Eugster, Simon Stücheli, Christoph Schultheiß, Corinne Widmer, Dominik Heim, Benjamin Kasenda, Jakob Passweg, Sebastian Kobold, Lukas Egli, Nicolò Coianiz, Obinna Chijioke, Nicholas Chiorazzi, Marie Follo, Heinz Läubli, Matthias Peipp, Mascha Binder","doi":"10.3324/haematol.2025.287697","DOIUrl":"https://doi.org/10.3324/haematol.2025.287697","url":null,"abstract":"We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors. R110-bsAb spared polyclonal human B cells (as opposed to CD19-targeting Blinatumomab) as well as CD34+ human stem cells. Yet, R110- bsAb induced lower T cell activation than Blinatumomab with primary CLL cells likely due to lower expression of target antigen. In vivo, R110-bsAb specifically killed IGLV3-21R110-expressing cell lines and CLL cells while sparing peripheral blood mononuclear cells. These findings highlight bispecific antibodies as a potential off-the-shelf immunotherapy for high-risk CLL patients, offering selective targeting while preserving healthy B cells.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Distinct interleukin-6 production in IPL and TAFRO subtypes of idiopathic multicentric Castleman disease. 特发性多中心Castleman病IPL和TAFRO亚型中不同的白细胞介素-6产生

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.288147

Asami Nishikori,Midori Filiz Nishimura,Yoshito Nishimura,Rio Yamada,Tomoka Haratake,Daisuke Ennishi,Ryota Chijimatsu,Toshihiro Ito,Tomohiro Koga,Sayaka Ochi,Yuri Kawahara,Himawari Ueta,Yudai Takeda,Michael V Gonzalez,David C Fajgenbaum,Frits Van Rhee,Shuji Momose,Yasuharu Sato

{"title":"Distinct interleukin-6 production in IPL and TAFRO subtypes of idiopathic multicentric Castleman disease.","authors":"Asami Nishikori,Midori Filiz Nishimura,Yoshito Nishimura,Rio Yamada,Tomoka Haratake,Daisuke Ennishi,Ryota Chijimatsu,Toshihiro Ito,Tomohiro Koga,Sayaka Ochi,Yuri Kawahara,Himawari Ueta,Yudai Takeda,Michael V Gonzalez,David C Fajgenbaum,Frits Van Rhee,Shuji Momose,Yasuharu Sato","doi":"10.3324/haematol.2025.288147","DOIUrl":"https://doi.org/10.3324/haematol.2025.288147","url":null,"abstract":"Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), exhibit distinct pathophysiologic mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, the differences in IL-6 production sources between subtypes remain unclear. We examined the source of IL-6 production and its transcriptional regulation across iMCD subtypes using immunohistochemistry (IHC), in situ hybridization (ISH), and gene expression profiling. IHC and ISH revealed that plasma cells were the predominant IL-6-expressing cells in iMCD-IPL, whereas vascular endothelial cells expressed IL-6 in iMCD-TAFRO. Plasma cells in iMCD-IPL exhibited stronger IL-6 protein expression than in iMCD-TAFRO. Gene expression analysis revealed upregulation of XBP1, MZB1, DERL3, SSR4, FKBP11, FKBP2, PIM2, RABAC1, and SDF2L1 in iMCD-IPL, implying endoplasmic reticulum stress and plasma cell differentiation in IL-6 dysregulation. Our findings suggest that XBP1-mediated IL-6 production may contribute to iMCD-IPL pathogenesis, potentially explaining its favorable responses to IL-6 blockade therapy. In contrast, IL-6 production in iMCD-TAFRO may be predominantly from vascular endothelial cells, suggesting that elevated serum IL-6 is a secondary phenomenon of the cytokine storm in this subtype. Future studies should clarify how proteomics and gene expression profiling can inform subtype-specific therapeutic strategies in iMCD.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"42 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.288004

Koji Kawamura,Junya Kanda,Sachiko Seo,Fumihiko Kimura,Masahiro Hirayama,Naoyuki Uchida,Noriko Doki,Wataru Takeda,Tetsuya Nishida,Yuta Katayama,Masatsugu Tanaka,Masashi Sawa,Satoshi Yoshihara,Tetsuya Eto,Toshiro Kawakita,Hirohisa Nakamae,Shuichi Ota,Fumihiko Ishimaru,Takahiro Fukuda,Yoshiko Atsuta,Yoshinobu Kanda

引用次数: 0

Blinatumomab restores asparaginase activity in pediatric B-cell acute lymphoblastic leukemia patients with PEG-Asparaginase hypersensitivity. Blinatumomab可恢复小儿b细胞急性淋巴细胞白血病peg -天冬酰胺酶过敏患者的天冬酰胺酶活性。

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.287910

Xue Tang,Lingying Zhao,Wujiao Li,Shilin Liu,Xuejuan Li,Lixiang Zhu,Duocai Wang,Shiyang Chen,Zhaonan Liu,Sixi Liu,Feiqiu Wen,Oussama Abla,Ying Wang,Huirong Mai,Xiaoying Fu

引用次数: 0

Do high-volume centers really save more lives? A call for scientific rigor and transparency. Response to Comment on: Does size matter? Center-specific characteristics and survival after allogeneic hematopoietic cell transplantation for acute myeloid leukemia: an analysis of the German Registry for Stem Cell Transplantation and Cell Therapy. 高容量中心真的能挽救更多生命吗？呼吁科学的严谨性和透明度。评论：大小重要吗？同种异体造血细胞移植治疗急性髓性白血病后的中心特异性特征和存活率：德国干细胞移植和细胞治疗登记处的分析。

IF 7.9 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.288957

Wolfgang Bethge, Peter Dreger

引用次数: 0

Splenic erythrophagocytosis is regulated by ALX/FPR2 signaling. 脾红细胞吞噬是由ALX/FPR2信号调控的。

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.288007

Haley Asplund,Hector H Dreyer,Jing-Juan Zheng,Richa Singhal,Jason L Hellmann,Brian E Sansbury

{"title":"Splenic erythrophagocytosis is regulated by ALX/FPR2 signaling.","authors":"Haley Asplund,Hector H Dreyer,Jing-Juan Zheng,Richa Singhal,Jason L Hellmann,Brian E Sansbury","doi":"10.3324/haematol.2025.288007","DOIUrl":"https://doi.org/10.3324/haematol.2025.288007","url":null,"abstract":"Maintaining a healthy pool of circulating red blood cells (RBCs) is essential for adequate perfusion, as even minor changes in the population can impair oxygen delivery, resulting in serious health complications including tissue ischemia and organ dysfunction. This responsibility largely falls to specialized macrophages in the spleen, known as red pulp macrophages, which efficiently take up and recycle damaged RBCs. However, questions remain regarding how these macrophages are acutely activated to accommodate increased demand. Proresolving lipid mediators stimulate macrophage phagocytosis and efferocytosis but their role in erythrophagocytosis has only recently been described. To investigate the role of lipid mediators on red pulp macrophage function, we targeted the ALX/FPR2 signaling pathway, as this receptor binds multiple lipid mediator ligands eliciting potent macrophage responses. We found that mice with Fpr2 deletion exhibited disrupted erythrocyte homeostasis resulting in an aged RBC pool, decreased markers of splenic RBC turnover, and altered splenic macrophage phenotype characterized by changes in heme metabolism. Upon activation of ondemand erythrophagocytosis, production of the ALX/FPR2 ligand, lipoxin A4 (LXA4), was induced in the spleen while receptor-deficient animals were unable to efficiently clear damaged RBCs, a defect that was conserved in mice with myeloid-specific FPR2 deletion. Similarly, mice lacking the LXA4 biosynthetic enzyme displayed defective erythrophagocytosis that was rescued with LXA4 administration. These results indicate that the ALX/FPR2 signaling axis is necessary for maintenance of RBC homeostasis and LXA4 activation is a critical aspect of the red pulp macrophage response to acute erythroid stress.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"35 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Early cytokine and chemokine signals shape the anti-AML activity of bispecific engager-secreting T cells. 早期细胞因子和趋化因子信号塑造双特异性接合分泌T细胞的抗aml活性。

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.287934

Natalie J Holl,Adam Fearnow,Ilias Christodoulou,Stamatia C Vorri,Ruyan Rahnama,Jun Choe,Alokesh Ghosal,Weng-Ian Ng,Vinay Vyas,Hannah W Song,Ravi Varadhan,Challice L Bonifant

{"title":"Early cytokine and chemokine signals shape the anti-AML activity of bispecific engager-secreting T cells.","authors":"Natalie J Holl,Adam Fearnow,Ilias Christodoulou,Stamatia C Vorri,Ruyan Rahnama,Jun Choe,Alokesh Ghosal,Weng-Ian Ng,Vinay Vyas,Hannah W Song,Ravi Varadhan,Challice L Bonifant","doi":"10.3324/haematol.2025.287934","DOIUrl":"https://doi.org/10.3324/haematol.2025.287934","url":null,"abstract":"Immunotherapies, including cell therapies, are effective anti-cancer agents. However, cellular product persistence can be limiting with short functional duration of activity contributing to disease relapse. A variety of manufacturing protocols are used to generate therapeutic engineered T-cells; these differ in techniques used for T-cell isolation, activation, genetic modification, and other methodology. We sought to determine how preselection affected the phenotype of T cells engineered to secrete a CD123xCD3 bispecific engager (ENG-T). These cells were designed to treat acute myeloid leukemia (AML). We evaluated the effect of T-cell selection on transduction efficiency, T-cell activation, short- and long-term anti-AML cytotoxicity, and gene transcription. Unselected, CD4, CD8, and CD4/CD8 pre-selected ENG-T cells have minor differences in T-cell subset components, equivalent activation, and equal cytotoxicity in short-term assays. While unselected and CD4/CD8-selected ENG-T cells have identical CD4:CD8 composition prior to target cell exposure, serial stimulation in vitro showed CD4/CD8 pre-selection supports ENG-T cell survival and long-term activity. Likewise, CD4 and CD4/CD8 pre-selected ENG-T cells display superior anti-tumor efficacy and prolong murine survival in AML xenografts. Unselected ENG-T cells are exposed to cytokines during early manufacture that imprint upregulation of intracellular inflammatory pathways. This early activation likely underpins long-term observed functional differences. Pre-selection of T cells from banked patient biospecimens decreased blast contamination, exposure to inflammatory cytokines, and may improve T-cell expansion during manufacture. Pre-selection of T-cell products should continue to be performed to enhance the quality of clinical cellular therapeutics.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"10 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Immune intervention is dispensable for retinoic acid/arsenic therapy of murine acute promyelocytic leukemia. 维甲酸/砷治疗小鼠急性早幼粒细胞白血病需要免疫干预。

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.288562

Cécile Esnault,Gael Fortin,Fang Qiu,Hassane Soilihi,Sylvie Souquère,Michiko Niwa-Kawakita,Kassandra Lanchais,Thassadite Dirami,Gérard Pierron,Hugues De Thé

引用次数: 0

HLA matching in the PTCy era: the locus still matters. Comment on: Selection of unrelated donors for allogeneic transplantation using post-transplant cyclophosphamide in acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. PTCy时代的HLA匹配：基因座仍然很重要。点评：选择非亲属供体进行急性淋巴细胞白血病移植后环磷酰胺异体移植：欧洲血液和骨髓移植学会急性白血病工作组的一项分析。

IF 10.1 1区医学

Haematologica Pub Date : 2025-09-11 DOI: 10.3324/haematol.2025.289055

Nihar Desai,Jonas Mattsson

引用次数: 0