Blood最新文献

{"title":"From prognostication to precision in acute myeloid leukemia.","authors":"Christopher S Hourigan","doi":"10.1182/blood.2024028105","DOIUrl":"https://doi.org/10.1182/blood.2024028105","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"35 1","pages":"2105-2106"},"PeriodicalIF":20.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921065","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}

{"title":"Epigenetics-based stratification in pediatric T-ALL.","authors":"Mathieu Simonin, Aurore Touzart","doi":"10.1182/blood.2024028016","DOIUrl":"https://doi.org/10.1182/blood.2024028016","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"145 19","pages":"2108-2110"},"PeriodicalIF":21.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976309","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}

{"title":"How I treat AML relapse after allogeneic HSCT.","authors":"Mahasweta Gooptu, H Moses Murdock, Robert J Soiffer","doi":"10.1182/blood.2024025705","DOIUrl":"10.1182/blood.2024025705","url":null,"abstract":"<p><strong>Abstract: </strong>Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the principal curative approaches in the treatment of acute myeloid leukemia (AML); however, relapse after transplantation remains a catastrophic event with poor prognosis. The incidence of relapse has remained unchanged over the last 3 decades despite an evolving understanding of the immunobiology of the graft-versus-leukemia effect and the immune escape mechanisms that lead to post-HSCT relapse. The approach to posttransplant relapse is highly individualized and is dictated both by disease biology and genomics as well as the patient's clinical status at the time of relapse and the interval between relapse and transplantation. With the help of 3 illustrative cases, we discuss our approach to early, late, and incipient relapse. Current therapeutic strategies incorporate immunosuppression taper when feasible, a variety of targeted and nontargeted chemotherapeutic agents, and consolidative cellular therapies including donor lymphocyte infusions or a second allogeneic transplant. We then summarize evolving frontiers in the treatment and prognostication of relapse, including the critical role of measurable residual disease. Finally, we emphasize enrollment on clinical trials and thoughtful discussions regarding goals of care and supporting frail patients as universal principles that should be incorporated in approaches to treatment of AML relapse after transplantation.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2128-2137"},"PeriodicalIF":21.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885123","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}

{"title":"Clonal γδ T-cell proliferation associated with Babesia infection: a rare and challenging diagnostic pitfall.","authors":"Habibe Kurt,Sam Sadigh","doi":"10.1182/blood.2025028400","DOIUrl":"https://doi.org/10.1182/blood.2025028400","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"18 1","pages":"2229"},"PeriodicalIF":20.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921056","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}

{"title":"GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia.","authors":"Fatemeh Alikarami, Hongbo M Xie, Simone S Riedel, Haley T Goodrow, Declan R Barrett, Leila Mahdavi, Alexandra Lenard, Changya Chen, Taylor Yamauchi, Etienne Danis, Zhendong Cao, Vu L Tran, Mabel Minji Jung, Yapeng Li, Hua Huang, Junwei Shi, Kai Tan, David T Teachey, Emery H Bresnick, Tobias A Neff, Kathrin M Bernt","doi":"10.1182/blood.2024025761","DOIUrl":"10.1182/blood.2024025761","url":null,"abstract":"<p><strong>Abstract: </strong>Stemness-associated cell states are linked to chemotherapy resistance in acute myeloid leukemia (AML). We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance. We find substantial intrapatient and interpatient variability in GATA2 expression across samples from patients with AML. GATA2 expression varies by molecular subtype and has been linked to outcome. In a murine model, KMT2A-MLL3-driven AML originating from a stem cell or immature progenitor cell population has higher Gata2 expression and is more resistant to the standard AML chemotherapy agent doxorubicin. Deletion of Gata2 resulted in a more robust induction of p53 after exposure to doxorubicin. Chromatin immunoprecipitation sequencing, RNA sequencing, and functional studies revealed that GATA2 regulates the expression of RASSF4, a modulator of the p53 inhibitor MDM2 (mouse double minute 2). GATA2 and RASSF4 are anticorrelated in human cell lines and in bulk and single-cell expression data sets from patients with AML. Knockdown of Rassf4 in Gata2-low cells resulted in doxorubicin or nutlin-3 resistance. Conversely, overexpression of Rassf4 results in sensitization of cells expressing high levels of Gata2. Finally, doxorubicin and nutlin-3 are synergistic in Gata2-high murine AML and in samples from patients with AML. We discovered a previously unappreciated role for GATA2 in dampening p53-mediated apoptosis via transcriptional regulation of RASSF4, a modulator of MDM2. This role for GATA2 directly links the expression of a stemness-associated transcription factor to chemotherapy resistance.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2179-2195"},"PeriodicalIF":21.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999660","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}

{"title":"EMZL at various sites: learning from each other.","authors":"Ming-Qing Du","doi":"10.1182/blood.2024025794","DOIUrl":"10.1182/blood.2024025794","url":null,"abstract":"<p><strong>Abstract: </strong>Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) invariably develops from a background of chronic inflammatory disorder caused by a diverse chronic microbial infection and/or autoimmunity, depending on the site. These chronic inflammatory/autoimmunity disorders trigger innate and acquired immune responses, generating a unique microenvironment at each site that drives clonal evolution of B cells, their expansion, and eventual malignant transformation. At a molecular level, this involves temporal and spatial acquisition of cooperative oncogenic events by dysregulated immune responses and somatic genetic changes. Although these events are not yet fully characterized, EMZL at several sites shows distinct genetic profiles and molecular insights, bridging the pathologic process to lymphomagenesis. For example, gastric EMZL, particularly those lacking a BCL10 or MALT1 translocation, critically depends on T-helper cell signals produced by immune responses to Helicobacter pylori infection. Likewise, thyroid EMZL may also involve exaggerated T-cell help because of highly frequent inactivating mutations in TET2, CD274 (programmed cell death 1 ligand 1), and TNFRSF14, which impede the coinhibitory interactions between the neoplastic B- and T-helper cells, thus releasing T-cell help. Ocular adnexal EMZL shows frequent TNFAIP3 (A20) mutation/deletion that significantly associates with expression of autoreactive IGHV4-34 B-cell receptor, emphasizing its potential cooperation in NF-κB pathway activation. Finally, the genesis of salivary gland EMZL may be closely associated with GPR34 activation that is caused by mutation/t(X;14)(p11;q32) and/or paracrine stimulation mediated by ligand generated by lymphoepithelial lesions. This review will focus on these novel molecular insights and how these advances may provide a paradigm for future investigations.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2117-2127"},"PeriodicalIF":21.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254997","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}

{"title":"Myelodysplastic neoplasm with biallelic TP53 inactivation in a patient with plasma cell myeloma after cytotoxic therapy.","authors":"Rong He,Dong Chen","doi":"10.1182/blood.2024028288","DOIUrl":"https://doi.org/10.1182/blood.2024028288","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"68 1","pages":"2230"},"PeriodicalIF":20.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921055","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}

{"title":"ANKRD26-related Thrombocytopenia 2 with a Baseline Increase in Blasts: Implications for Clinical Surveillance.","authors":"Lara Wahlster,Lucy A Godley,Jason X Cheng,Michael W Drazer,Christopher R Reilly,Geraldine S Pinkus,Jared H Rowe,Nina Weichert-Leahey,Robert Grant Rowe,Lev Gorfinkel,Karyn Jean Brundige,Franziska Wachter,Luana Miria Messa,Alan D Michelson,Alan B Cantor,Akiko Shimamura,Jacob R Bledsoe","doi":"10.1182/blood.2024027368","DOIUrl":"https://doi.org/10.1182/blood.2024027368","url":null,"abstract":"We report eight patients with ANKRD26-related thrombocytopenia-2 (ANKRD26-RT) with elevated bone marrow myeloblasts and dysmegakaryopoiesis, without somatic genetic abnormalities or progression to malignancy during long-term observation, findings which may constitute inherent ANKRD26-RT biology rather than progression to myeloid malignancy.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"1 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914973","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}

{"title":"Novel, potent, and orally bioavailable LSD1 inhibitors induce fetal hemoglobin synthesis in a sickle cell disease mouse model.","authors":"Yu Wang,Lei Yu,Kaiwen Deng,Mathivanan Packiarajan,Angelo Aguilar,Sojin An,Greggory Myers,Hoon Oh,Sharon A Singh,Uhn-Soo Cho,Shaomeng Wang,Yuanfang Guan,Andrew White,Rami Khoriaty,James Douglas Engel","doi":"10.1182/blood.2024028006","DOIUrl":"https://doi.org/10.1182/blood.2024028006","url":null,"abstract":"Small molecules that inhibit LSD1 (lysine-specific demethylase 1, KDM1A) have been shown to induce abundant fetal hemoglobin (HbF) levels in red blood cells both in vitro and in vivo, therefore potentially serving as potent and cost-effective therapeutics to treat the β-globinopathies, sickle cell disease (SCD) and β-thalassaemia major (TM). However, most LSD1 inhibitors (LSD1i) that induce HbF in vivo are covalent and irreversible, which leads to adverse effects. In this study, we utilized structure-aided drug design to develop potent new reversible LSD1i's leading to robust γ-globin expression in vitro. Moreover, in a mouse model of SCD, oral administration of these novel inhibitors lead to significant HbF elevation and alleviation of multiple features of disease pathology that are the usual consequences of SCD. In addition, we discovered that combined treatment of an LSD1i with a BRD4 degrader (BD-9136) represses the induction of RUNX1 and PU.1, thereby rescuing the erythroid to myeloid lineage conversion that accompanies LSD1i in hematopoiesis. The data indicate that this new generation of LSD1i can effectively induce HbF levels, reduce SCD pathologies, and are well-tolerated by oral administration in SCD mice. We anticipate that the combination of these or related binary compounds offer exciting new therapeutic possibilities for treating SCD and TM.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"2 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915086","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}

{"title":"Augmented CD47 expression impairs alloreactive T-cell clearance after allo-HCT.","authors":"Cindy Sheree Flamann,Haroon Shaikh,Carina Matos,Marina Kreutz,Hla Ali,Michael Ag Kern,Maike Büttner-Herold,Benedikt Jacobs,Simon Völkl,Christopher Lischer,Christian Kellner,Johannes Berges,Katrin Bitterer,Domenica Saul,Manisha Goel,Cornelia Link-Rachner,Alma Zernecke,Daniela Andrea Weber,Dimitrios Mougiakakos,Andreas Mackensen,Andreas Beilhack,Heiko Bruns","doi":"10.1182/blood.2023023056","DOIUrl":"https://doi.org/10.1182/blood.2023023056","url":null,"abstract":"Graft-versus-Host disease (GvHD) ensues as the most common non-relapse complication after allogeneic hematopoietic cell transplantation (allo-HCT). A pivotal goal in GvHD management revolves around quelling inflammation. Phagocytic clearance of inflammatory cells contributes substantially to termination of inflammatory processes. Nevertheless, the precise functions of phagocytosis in GvHD remain largely unclear. In this study, we identified the \"don't eat me\"-signal CD47 as a promising target for therapeutic interventions aimed at eradicating alloreactive T-cells subsequent to allo-HCT. Analysis of global data sets revealed a remarkable upregulation of CD47 expression on T-cells residing in the ileum of patients with inflamed intestine. Building on this finding, we examined CD47 levels in the gastrointestinal tract (GIT) following allo-HCT. Our work not only confirmed upregulated CD47 expression in the GIT of GvHD patients, but also identified CD47 on T-cells in the ileum of GvHD mice after allo-HCT. Additionally, we found that activated donor T-cells suppress antibody-dependent cellular phagocytosis (ADCP) via CD47 signaling in vitro. Application of anti-CD47 antibodies significantly invigorated the impaired ADCP of activated T-cells. Administering anti-CD47 antibodies to mice elevated phagocytosis of T-cells in the GIT, induced immunosuppressive responses and improved survival. Finally, transplantation of CD47 deficient donor T-cells significantly improved clinical GvHD score with improved survival after allo-HCT. Collectively, our findings illuminate CD47 upregulation as pivotal mechanism in GvHD patients, leading to impaired phagocytic clearance of alloreactive T-cells. This study proposes that anti-CD47 treatment could rectify the compromised phagocytosis of alloreactive T-cells, thereby aiding in the resolution of inflammation after allo-HCT.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"2675 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915083","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}