Leukemia最新文献

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Correction: Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML. 更正:纵向单细胞分析揭示了治疗耐药的干细胞和肥大细胞与儿科AML的潜在治疗方法。
IF 13.4 1区 医学
Leukemia Pub Date : 2025-09-19 DOI: 10.1038/s41375-025-02773-6
Denis Ohlstrom, Mojtaba Bakhtiari, Hope Mumme, Marina Michaud, Alejandro De Janon Gutierrez, Deborah DeRyckere, Katherine E Ferguson, Frank Chien, William Pilcher, Sarthak Satpathy, Sean Jordan, Douglas Graham, Swati Bhasin, Manoj Bhasin
{"title":"Correction: Longitudinal single-cell analysis reveals treatment-resistant stem and mast cells with potential treatments for pediatric AML.","authors":"Denis Ohlstrom, Mojtaba Bakhtiari, Hope Mumme, Marina Michaud, Alejandro De Janon Gutierrez, Deborah DeRyckere, Katherine E Ferguson, Frank Chien, William Pilcher, Sarthak Satpathy, Sean Jordan, Douglas Graham, Swati Bhasin, Manoj Bhasin","doi":"10.1038/s41375-025-02773-6","DOIUrl":"https://doi.org/10.1038/s41375-025-02773-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092074","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
Clonal evolution and apoptosis resistance in myelodysplastic neoplasms and acute myeloid leukemia under treatment: insights from integrative longitudinal profiling. 骨髓增生异常肿瘤和急性髓系白血病在治疗中的克隆进化和细胞凋亡抵抗:来自综合纵向分析的见解。
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-19 DOI: 10.1038/s41375-025-02756-7
Paolo Mazzeo,Sarah Mae Penir,Evgenii Shumilov,Sebastian Wolf,Björn Häupl,Katharina Markus,Katayoon Shirneshan,Katharina Rittscher,Elzbieta Brzuszkiewicz,Enver Aydilek,Hannes Treiber,Thomas Oellerich,Christina Ganster,Detlef Haase,Raphael Koch
{"title":"Clonal evolution and apoptosis resistance in myelodysplastic neoplasms and acute myeloid leukemia under treatment: insights from integrative longitudinal profiling.","authors":"Paolo Mazzeo,Sarah Mae Penir,Evgenii Shumilov,Sebastian Wolf,Björn Häupl,Katharina Markus,Katayoon Shirneshan,Katharina Rittscher,Elzbieta Brzuszkiewicz,Enver Aydilek,Hannes Treiber,Thomas Oellerich,Christina Ganster,Detlef Haase,Raphael Koch","doi":"10.1038/s41375-025-02756-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02756-7","url":null,"abstract":"Treatment of high-risk Myelodysplastic Neoplasms (hr-MDS) and (secondary) Acute Myeloid Leukemia (AML) remains a clinical challenge. The combination of azacitidine and venetoclax (aza/ven) may improve treatment outcomes, but still fails in a significant fraction of patients. We established a single-center collection of longitudinal samples from patients with MDS and AML/sAML and performed comprehensive genetic, proteomic and functional apoptosis profiling to identify biomarkers and targetable escape mechanisms to aza/ven. Baseline genetic characterization (n = 55) identified high-risk genetic alterations, while longitudinal analyses (n = 268, mean 8.7 [3-20] timepoints) revealed distinct genetic profiles of clonal evolution. Functional BH3-profiling at treatment initiation identified heterogeneous dependencies on BCL-2 family members. Notably, high BCL-2 dependence correlated with genetic response to aza/ven and improved overall survival, whereas increased BCL-xL dependence was associated with resistance. We further identified patterns of acquired resistance, with loss of apoptotic priming and shifts in anti-apoptotic dependencies contributing to treatment failure. BH3 profiling revealed functional shifts toward MCL-1 and/or BCL-xL in individual cases, suggesting potential therapeutic targets to overcome resistance. In vitro, BCL-xL inhibition effectively counteracted resistance in increased BCL-xL dependence cases. In summary, we characterized treatment-associated clonal evolution in MDS and AML, providing insights into clinical response, disease progression and potential individualized therapeutic strategies.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"24 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089838","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
Suppression of Rho-associated kinase 1 (ROCK1) promotes human hematopoietic stem cell expansion by attenuating mitochondrial fission rho相关激酶1 (ROCK1)的抑制通过减弱线粒体裂变促进人造血干细胞的扩增
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-16 DOI: 10.1038/s41375-025-02770-9
Xuepeng Wang, Baskar Ramdas, Ramesh Kumar, Ji Zhang, Reuben Kapur
{"title":"Suppression of Rho-associated kinase 1 (ROCK1) promotes human hematopoietic stem cell expansion by attenuating mitochondrial fission","authors":"Xuepeng Wang, Baskar Ramdas, Ramesh Kumar, Ji Zhang, Reuben Kapur","doi":"10.1038/s41375-025-02770-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02770-9","url":null,"abstract":"Ex vivo expansion of hematopoietic stem cells (HSCs) is limited by mitochondrial stress-induced loss of stemness. To identify protective mechanisms resembling the hypoxic bone marrow niche, we performed single-cell transcriptomics on hypoxia-collected HSCs, revealing significant downregulation of Rho-associated kinase 1 (ROCK1). This observation suggested ROCK1 as a potential regulator of HSC homeostasis. We tested this by genetically or pharmacologically inhibiting ROCK1 with shRNA or Y27632, which reduced mitochondrial reactive oxygen species, mitochondrial mass, and membrane potential while promoting expansion of phenotypic HSCs (Lin⁻CD34⁺CD38⁻CD45RA⁻CD49f⁺CD90⁺). Mechanistically, ROCK1 inhibition attenuated DRP1-mediated mitochondrial fission by decreasing p-DRP1(Ser616) and increasing p-DRP1(Ser637), thereby reducing mitochondrial fragmentation. Additionally, ROCK1 inhibition elevated BCL2 expression and reduced active Caspase-3 levels, indicating suppressed apoptosis. Limiting dilution transplants demonstrated a fourfold increase in functional HSC frequency following ROCK1 inhibition, with enhanced long-term engraftment in secondary recipients. Our findings identify ROCK1 as a critical regulator of mitochondrial dynamics in HSCs and provide a mechanistic basis for targeting ROCK1 to enhance functional HSC expansion, offering a promising strategy to improve outcomes in HSC transplantation by mimicking hypoxic niche signals ex vivo.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"42 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068054","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
Granulocyte abundance and maturation state at diagnosis predicts treatment-free remission in CML 诊断时的粒细胞丰度和成熟状态预测CML的无治疗缓解
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-16 DOI: 10.1038/s41375-025-02769-2
Mikko Purhonen, Mikael Tatun, Katariina Luukkainen, Kevin Hung, Henri Sundquist, Oda Tafjord, Stina Söderlund, Shady Adnan-Awad, Anni Dohlen, Johanna Heikkinen, Perttu Koskenvesa, Sanna Siitonen, Satu Mustjoki, Naranie Shanmuganathan, Coral Bryce, Signe Danielsson, Henrik Hjorth-Hansen, Ulla Olsson-Strömberg, Takashi Kumagai, Shinya Kimura, David M. Ross, Oscar Brück
{"title":"Granulocyte abundance and maturation state at diagnosis predicts treatment-free remission in CML","authors":"Mikko Purhonen, Mikael Tatun, Katariina Luukkainen, Kevin Hung, Henri Sundquist, Oda Tafjord, Stina Söderlund, Shady Adnan-Awad, Anni Dohlen, Johanna Heikkinen, Perttu Koskenvesa, Sanna Siitonen, Satu Mustjoki, Naranie Shanmuganathan, Coral Bryce, Signe Danielsson, Henrik Hjorth-Hansen, Ulla Olsson-Strömberg, Takashi Kumagai, Shinya Kimura, David M. Ross, Oscar Brück","doi":"10.1038/s41375-025-02769-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02769-2","url":null,"abstract":"<p>Treatment-free remission (TFR) has become a therapeutic objective for selected chronic-phase chronic myeloid leukemia (CP CML). However, no standardized biomarker is yet in clinical use. In this multi-center study, we explored the potential of bone marrow (BM) cytomorphology given its global accessibility and integral role in clinical diagnostics. We included diagnostic BM aspirate samples of 113 CP CML patients from seven clinical sites having attempted first TKI discontinuation. We digitized cytomorphological slides into 100x-magnified high-resolution images and analyzed these with deep learning-based image analysis. We profiled the BM cytomorphological fingerprint of CP CML patients and recapitulated the known granulocytic predominance and reduction of lymphoid, monocytic and erythroid cells in comparison to an extensive cohort of 942 control BM samples. We discovered neutrophil abundance and granulocytic maturation to associate with sustained TFR. We confirmed these visually and demonstrated their independent impact over known clinical factors. Our study underlines the potential of computational BM cytomorphology to identify novel clinical biomarkers and suggests that granulocytic expansion and maturation at diagnosis could reflect intrinsic disease pathology influencing TFR maintenance.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"36 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068055","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
Downregulation of MICA/MICB improves cell persistence and clinical activity of NKG2DL CAR T-cells in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic neoplasia MICA/MICB下调可改善复发或难治性急性髓性白血病或骨髓增生异常瘤患者NKG2DL CAR - t细胞的细胞持久性和临床活性
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-15 DOI: 10.1038/s41375-025-02767-4
Daniel Pollyea, Tessa Kerre, Dries Deeren, Yves Beguin, Tara L. Lin, David A. Sallman, Sebastien Anguille, William G. Blum, Anne Flament, Eytan Breman, Caroline Lonez
{"title":"Downregulation of MICA/MICB improves cell persistence and clinical activity of NKG2DL CAR T-cells in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic neoplasia","authors":"Daniel Pollyea, Tessa Kerre, Dries Deeren, Yves Beguin, Tara L. Lin, David A. Sallman, Sebastien Anguille, William G. Blum, Anne Flament, Eytan Breman, Caroline Lonez","doi":"10.1038/s41375-025-02767-4","DOIUrl":"https://doi.org/10.1038/s41375-025-02767-4","url":null,"abstract":"<p>The NKG2D receptor binds eight ligands (NKG2DL) overexpressed in a wide range of malignancies, but largely absent on non-neoplastic cells. Initial clinical evaluation of NKG2DL chimeric antigen receptor (CAR) T-cells (CYAD-01) in patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) or myelodysplastic neoplasia (MDS) demonstrated low durability of responses and short cell persistence. Two Phase I trials were initiated to evaluate the effect of lymphodepletion prior to a single CAR T-cell infusion in a similar r/r AML/MDS patient population. The DEPLETHINK trial (NCT03466320) evaluated CYAD-01 while the CYCLE-1 trial (NCT04167696) evaluated a next-generation NKG2DL CAR, CYAD-02, where the two main NKG2D ligands MICA and B are downregulated, to increase CAR T-cell persistence. Seventeen and twelve patients were treated in the DEPLETHINK and CYCLE-1 trials, and confirmed the good tolerability of both products with cytokine release syndrome (CRS) grade 3 or 4 reported in 25% and 33.3% of patients, respectively. CYAD-02 presented an higher engraftment and an improved clinical activity (17% objective response rate) compared to CYAD-01 (no objective response). Altogether, our data provide proof of principle that knock-down of MICA/B can enhance CAR T-cell persistence and efficacy while maintaining a good safety profile.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"35 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059612","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
CRISPR-engineered human GATA2 deficiency model uncovers mitotic dysfunction and premature aging in HSPCs, impairing hematopoietic fitness crispr工程人类GATA2缺陷模型揭示HSPCs有丝分裂功能障碍和早衰,损害造血适应性
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-15 DOI: 10.1038/s41375-025-02771-8
Damia Romero-Moya, Eric Torralba-Sales, Cristina Calvo, Oskar Marin-Bejar, Maria Magallon-Mosella, Maximiliano Distefano, Joan Pera, Julio Castaño, Francesca De Giorgio, Jessica Gonzalez, Arnau Iglesias, Clara Berenguer-Balaguer, Marcel Schilling, Mireya Plass, Lorenzo Pasquali, Albert Català, Oscar Molina, Marcin W. Wlodarski, Anna Bigas, Alessandra Giorgetti
{"title":"CRISPR-engineered human GATA2 deficiency model uncovers mitotic dysfunction and premature aging in HSPCs, impairing hematopoietic fitness","authors":"Damia Romero-Moya, Eric Torralba-Sales, Cristina Calvo, Oskar Marin-Bejar, Maria Magallon-Mosella, Maximiliano Distefano, Joan Pera, Julio Castaño, Francesca De Giorgio, Jessica Gonzalez, Arnau Iglesias, Clara Berenguer-Balaguer, Marcel Schilling, Mireya Plass, Lorenzo Pasquali, Albert Català, Oscar Molina, Marcin W. Wlodarski, Anna Bigas, Alessandra Giorgetti","doi":"10.1038/s41375-025-02771-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02771-8","url":null,"abstract":"<p>GATA2 deficiency is a monogenic transcriptopathy disorder characterized by bone marrow failure (BMF), immunodeficiency, and a high risk of developing myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). Although informative mouse models have been developed, the mechanisms by which GATA2 haploinsufficiency drives disease initiation in humans remain incompletely understood. To address this, we developed a novel humanized model using CRISPR/Cas9 technology to knock-in GATA2-R398W variant in primary cord blood CD34⁺ cells. Additionally, we introduced specific mutations in SETBP1 and ASXL1 to model distinct premalignant stages of GATA2 deficiency. Through clonal competition and serial transplantation assays, we demonstrated that human CD34<sup>+</sup> cells harboring the GATA2 mutation exhibit significantly reduced fitness in vivo when compete with wild-type cells. Notably, this fitness disadvantage persists even when GATA2 mutations are combined with oncogenic SETBP1 and ASXL1 drivers, underscoring the dominant, deleterious effect of GATA2 deficiency on hematopoietic stem cell function. Functional in vitro analyses revealed that GATA2-R398W mutation impairs cell proliferation, disrupts cell cycle progression, and induces mitotic defects, which may contribute to hematopoietic stem/progenitor cell loss and impaired self-renewal. Transcriptomic profiles of GATA2-mutant cells revealed that these functional defects are associated with reduced HSC self-renewal capacity and upregulation of the pre-aging phenotype. Our work highlights the feasibility of generating a human GATA2 deficiency model suitable for studying the biological consequences of various GATA2 variants and the generation of a platform to test potential phenotype-rescuing therapeutics.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"29 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059611","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
Resolving inter- and intra-patient heterogeneity in NPM1-mutated AML at single-cell resolution 在单细胞分辨率下解决npm1突变AML患者间和患者内部异质性
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-15 DOI: 10.1038/s41375-025-02745-w
E. Onur Karakaslar, Eva M. Argiro, Nadine E. Struckman, Ramin Shirali HZ, Jeppe F. Severens, M. Willy Honders, Susan L. Kloet, Hendrik Veelken, Marcel JT Reinders, Marieke Griffioen, Erik B. van den Akker
{"title":"Resolving inter- and intra-patient heterogeneity in NPM1-mutated AML at single-cell resolution","authors":"E. Onur Karakaslar, Eva M. Argiro, Nadine E. Struckman, Ramin Shirali HZ, Jeppe F. Severens, M. Willy Honders, Susan L. Kloet, Hendrik Veelken, Marcel JT Reinders, Marieke Griffioen, Erik B. van den Akker","doi":"10.1038/s41375-025-02745-w","DOIUrl":"https://doi.org/10.1038/s41375-025-02745-w","url":null,"abstract":"<p><i>NPM1-</i>mutated AML is one of the largest entities in international classification systems of myeloid neoplasms, which are based on integrating morphologic and clinical data with genomic data. Previous research, however, indicates that bulk transcriptomics-based subtyping may improve prognostication and therapy guidance. Here, we characterized the heterogeneity in <i>NPM1</i>-mutated AML by performing single-cell RNA-sequencing and spectral flow cytometry on 16 AML belonging to three distinct subtypes previously identified by bulk transcriptomics. Using single-cell expression profiling we generated a comprehensive atlas of <i>NPM1</i>-mutated AML, collectively reconstituting complete myelopoiesis. The three <i>NPM1</i>-mutated transcriptional subtypes showed consistent differences in the proportions of myeloid cell clusters with distinct patterns in lineage commitment and maturational arrest. In all samples, leukemic cells were detected across different myeloid cell clusters, indicating that <i>NPM1-</i>mutated AML are heavily skewed but not fully arrested in myelopoiesis. Same-sample multi-color spectral flow cytometry recapitulated these skewing patterns, indicating that the three <i>NPM1</i>-mutated subtypes can be consistently identified across platforms. Moreover, our analyses highlighted differences in the abundance of rare hematopoietic stem cells suggesting that skewing occurs early in myelopoiesis. To conclude, by harnessing single-cell RNA-sequencing and spectral flow cytometry, we provide a detailed description of three distinct and reproducible patterns in lineage skewing in <i>NPM1</i>-mutated AML that may have potential relevance for prognosis and treatment of patients with <i>NPM1</i>-mutated AML.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"63 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059610","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
DUX4-rearranged B-ALL: deciphering a biological and clinical conundrum dux4重排B-ALL:破解生物学和临床难题
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-12 DOI: 10.1038/s41375-025-02758-5
Jack Bakewell, Anthony V. Moorman, Sarra L. Ryan
{"title":"DUX4-rearranged B-ALL: deciphering a biological and clinical conundrum","authors":"Jack Bakewell, Anthony V. Moorman, Sarra L. Ryan","doi":"10.1038/s41375-025-02758-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02758-5","url":null,"abstract":"<p>The <i>DUX4</i> gene, located within repetitive subtelomeric arrays on chromosomes 4 and 10, plays a critical role in early embryogenesis and has been implicated in several human diseases, including facioscapulohumeral muscular dystrophy (FSHD) and cancer. In B-cell acute lymphoblastic leukemia (B-ALL), <i>DUX4</i> rearrangements (<i>DUX4</i>-r) define a distinct genomic subtype affecting 5–10% of cases, which is more frequent among older children and teenagers. These rearrangements produce truncated DUX4 proteins with neomorphic transcriptional activity, resulting in aberrant gene expression programs and alternative splicing that disrupt normal B-cell precursor development. Patients with <i>DUX4</i>-r B-ALL often present with poor initial treatment responses, though they typically achieve excellent long-term survival rates with intensive chemotherapy regimens. The cryptic nature of <i>DUX4</i> rearrangements has historically posed significant challenges to accurate detection, but recent advancements in next-generation sequencing technologies, including RNA and long-read sequencing, and improved immunophenotyping strategies—such as the use of CD371 as a surrogate marker—are enhancing diagnostic accuracy. This review explores the genetic and biological features of <i>DUX4</i> and its rearrangements, shedding light on their role in leukemogenesis and associated clinical outcomes. Additionally, we highlight emerging technologies that enable the detection of <i>DUX4</i>-r and discuss their implications for clinical use and research. An improved understanding of <i>DUX4</i> biology and its oncogenic potential may pave the way for novel treatment strategies, ultimately improving outcomes for patients with <i>DUX4</i>-r B-ALL.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"33 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035224","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
Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study 阴燃型多发性骨髓瘤感染风险增加:来自筛选iStopMM研究的结果
IF 11.4 1区 医学
Leukemia Pub Date : 2025-09-12 DOI: 10.1038/s41375-025-02762-9
Lærke Sloth Andersen, Ricardo Berenguer Navarro, Sara Ekberg, Sæmundur Rögnvaldsson, Marína Rós Levy, Ingigerður Sólveig Sverrisdóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri Ólafsson, Brian G. M. Durie, Stephen Harding, Ola Landgren, Thorvardur Jón Löve, Sigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir
{"title":"Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study","authors":"Lærke Sloth Andersen, Ricardo Berenguer Navarro, Sara Ekberg, Sæmundur Rögnvaldsson, Marína Rós Levy, Ingigerður Sólveig Sverrisdóttir, Brynjar Viðarsson, Páll Torfi Önundarson, Bjarni A. Agnarsson, Margrét Sigurðardóttir, Ingunn Þorsteinsdóttir, Ísleifur Ólafsson, Ásdís Rósa Þórðardóttir, Elías Eyþórsson, Ásbjörn Jónsson, Andri Ólafsson, Brian G. M. Durie, Stephen Harding, Ola Landgren, Thorvardur Jón Löve, Sigurður Yngvi Kristinsson, Sigrún Thorsteinsdóttir","doi":"10.1038/s41375-025-02762-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02762-9","url":null,"abstract":"<p>Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95% CI 1.07–1.73) and antibacterial prescriptions (HR 1.24, 95% CI 1.01–1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95% CI 1.00–1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"66 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035223","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
Molecular profiling and risk stratification in solitary bone plasmacytoma 孤立性骨浆细胞瘤的分子分析和风险分层
IF 13.4 1区 医学
Leukemia Pub Date : 2025-09-11 DOI: 10.1038/s41375-025-02699-z
Barbara Burroni, Stéphanie Harel, Raphaele Seror, Sophia Ascione, Youlia Kirova, Diane Damotte, Rakiba Belkhir, Thierry Lazure, Véronique Meignin, Justine Decroocq, Virginie Audard, Rudy Birsen, Lise Willems, Frédérique Larousserie, Patricia Franchi, Yoan Velut, Nicolas Chapuis, Laure Derrier, Salomon Manier, Bénédicte Deau-Fischer, Julien Henry, Luka Pavageau, Alexis Talbot, Bruno Royer, Didier Bouscary, Bertrand Arnulf, Jill Corre, Marguerite Vignon
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