Leukemia最新文献_第10页

MEK inhibitors are effective in Erdheim–Chester disease regardless of MAPK pathway mutations 无论MAPK通路突变如何，MEK抑制剂对Erdheim-Chester病都有效

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-23 DOI: 10.1038/s41375-025-02614-6

Francesco Pegoraro, Fleur Cohen-Aubart, Matthias Papo, Francesco Catamerò, Jerome Razanamahery, Zahir Amoura, Jean-François Emile, Augusto Vaglio, Julien Haroche

引用次数: 0

National cancer system metrics and leukemia outcomes: an analysis of global data for pediatric and adult patients 国家癌症系统指标和白血病结果：儿童和成人患者的全球数据分析

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-23 DOI: 10.1038/s41375-025-02598-3

James Fan Wu, Erin Jay G. Feliciano, Angelica Singh, Douglas Tremblay, Muhammad Bilal Abid, Edward Christopher Dee

{"title":"National cancer system metrics and leukemia outcomes: an analysis of global data for pediatric and adult patients","authors":"James Fan Wu, Erin Jay G. Feliciano, Angelica Singh, Douglas Tremblay, Muhammad Bilal Abid, Edward Christopher Dee","doi":"10.1038/s41375-025-02598-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02598-3","url":null,"abstract":"Globally, nearly 500,000 individuals were diagnosed with leukemia in 2022 alone [1]. In 2022, leukemia was among the top ten causes of cancer death in 71 countries in adults and the leading cause of cancer death in 96 countries in children [1, 2]. However, significant global heterogeneity exists in the incidence of various leukemias and their associated mortality [1, 3]. Less-resourced countries have been shown to have higher leukemia mortality-to-incidence ratios (MIR), highlighting health system inequities across countries [1]. For example, from 2010–2014, for pediatric acute lymphoblastic leukemia, the 5-year survival was 65.9% in Thailand versus 95.2% in Finland [3]. Survival disparities are mirrored among adults. From 2010–2014, for adult myeloid malignancies, the 5-year survival was 16.5% in Chile versus 57.5% in France [3].While global disparities in both pediatric and adult leukemia have been documented [1, 3], further work is needed to elucidate how to translate these findings into cancer health system strengthening measures at the national and global levels. A detailed understanding of the levers that drive these cancer-specific infrastructures may inform health system planning specific to leukemia. Therefore, we used global health system data from the World Health Organization, the World Bank, the DIrectory of RAdiotherapy Centers, the United Nations Development Program, and the International Agency for Research on Cancer (IARC) to evaluate predictors of improved pediatric and adult leukemia outcomes globally.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"9 1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862996","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

Complosome as a new intracellular regulatory network in both normal and malignant hematopoiesis 复合体在正常和恶性造血中作为一种新的细胞内调节网络

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-23 DOI: 10.1038/s41375-025-02613-7

Mariusz Z. Ratajczak, Adrian Konopko, Justyna Jarczak, Michalina Kazek, Janina Ratajczak, Magdalena Kucia

{"title":"Complosome as a new intracellular regulatory network in both normal and malignant hematopoiesis","authors":"Mariusz Z. Ratajczak, Adrian Konopko, Justyna Jarczak, Michalina Kazek, Janina Ratajczak, Magdalena Kucia","doi":"10.1038/s41375-025-02613-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02613-7","url":null,"abstract":"Hematopoietic cells and lymphocytes arise from a common stem cell for both lineages. This explains why similar signaling networks regulate the development and biological functions of these cells. One crucial regulatory mechanism involves interactions with soluble mediators of innate immunity, including activated elements of the complement cascade (ComC). For many years, ComC proteins were thought to be synthesized only in the liver and released into blood to be activated by one of the three proteolytic cascades. The regulatory effects of activated components of ComC on hematopoietic stem progenitor cells (HSPCs) and mature hematopoietic cells have been well demonstrated in the past. However, recent data indicate that complement proteins are also expressed in several cell types, including lymphocytes and innate immune cells. This intracellular complement network has been named the “complosome.” Recent evidence from our group shows that the complosome is also expressed in HSPCs and plays an important yet underappreciated role in the expansion, trafficking, and metabolism of these cells. We propose that the complosome, like its role in lymphocytes, is necessary for the optimal function of mitochondria in hematopoietic cells, including HSPCs. This opens a new area for investigation and potential pharmacological intervention into the complosome network in normal and malignant hematopoiesis.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"20 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862998","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 11.4 1区医学

Leukemia Pub Date : 2025-04-22 DOI: 10.1038/s41375-025-02621-7

Natalya Plakhova, Vasilios Panagopoulos, Melissa D. Cantley, Laura J. Trainor, Duncan R. Hewett, Kimberley C. Clark, Jo Gardiner, Angelina Yong, Cindy Lee, Noemi Horvath, Peter I. Croucher, Dimitrios Cakouros, Sheila A. Stewart, Stan Gronthos, Andrew C. W. Zannettino, Krzysztof M. Mrozik, Kate Vandyke

{"title":"Age-related mesenchymal stromal cell senescence is associated with progression from MGUS to multiple myeloma","authors":"Natalya Plakhova, Vasilios Panagopoulos, Melissa D. Cantley, Laura J. Trainor, Duncan R. Hewett, Kimberley C. Clark, Jo Gardiner, Angelina Yong, Cindy Lee, Noemi Horvath, Peter I. Croucher, Dimitrios Cakouros, Sheila A. Stewart, Stan Gronthos, Andrew C. W. Zannettino, Krzysztof M. Mrozik, Kate Vandyke","doi":"10.1038/s41375-025-02621-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02621-7","url":null,"abstract":"The risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) increases with advancing age, suggesting that progression may be influenced by age-related changes within the bone marrow (BM) microenvironment. We hypothesise that senescent mesenchymal stromal cells (MSCs), which accumulate in the BM with age, may contribute to MGUS progression to MM. Here, we show that, like BM MSCs from aged non-cancer controls, BM MSCs from both MM and MGUS patients exhibit a senescent phenotype characterised by enlarged, flattened morphology, increased β-galactosidase activity and CDKN2A expression, and decreased proliferation rate compared with BM MSCs from healthy young individuals. While coculture with BM MSCs suppresses the proliferative capacity of MM cell lines in vitro, induction of senescence via irradiation or replicative exhaustion in healthy MSCs relieves this suppression, compared with non-senescent MSCs. This may, in part, be attributable to upregulated expression of the BMP antagonist Gremlin1 in senescent MSCs, which facillitates MM cell proliferation. Notably, the risk of progression to MM was significantly elevated in MGUS patients with increased MSC senescence. Collectively, our data provide evidence that age-related accumulation of senescent MSCs may be a driver of MGUS to MM progression.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"41 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862953","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

Loss of NOL10 leads to impaired disease progression of NUP98::DDX10 leukemia 缺失 NOL10 会导致 NUP98::DDX10 白血病的疾病进展受阻

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-22 DOI: 10.1038/s41375-025-02607-5

Yutaka Shima, Kazutsune Yamagata, Yoko Kuroki, Kazuki Sasaki, Yukiko Aikawa, Issay Kitabayashi

引用次数: 0

Impact of myelodysplasia-related gene mutations and residual mutations at remission in venetoclax/azacitidine for AML venetoclax/ az胞苷治疗急性髓性白血病缓解时骨髓增生异常相关基因突变和残留突变的影响

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-21 DOI: 10.1038/s41375-025-02625-3

Yoshikazu Ikoma, Nobuhiko Nakamura, Yuto Kaneda, Hiroyuki Takamori, Tomokazu Seki, Nobuhiro Hiramoto, Junichi Kitagawa, Junya Kanda, Kei Fujita, Tetsuji Morishita, Yotaro Ochi, Shigeru Chiba, Nana Sasaki, Michiko Ichii, Kazunori Imada, Mizuki Watanabe, Masakatsu Hishizawa, Yasuko Miyahara, Yoshitomo Maesako, Yasuhiro Tanaka, Satoko Oka, Masaaki Tsuji, Satoshi Yoshihara, Kinuko Mitani, Yasunori Ueda, Toshiyuki Kitano, Mitsumasa Watanabe, Nobuo Sezaki, Tadakazu Kondo, Senji Kasahara, Akifumi Takaori-Kondo, Nobuhiro Kanemura, Seishi Ogawa, Yasuhito Nannya

{"title":"Impact of myelodysplasia-related gene mutations and residual mutations at remission in venetoclax/azacitidine for AML","authors":"Yoshikazu Ikoma, Nobuhiko Nakamura, Yuto Kaneda, Hiroyuki Takamori, Tomokazu Seki, Nobuhiro Hiramoto, Junichi Kitagawa, Junya Kanda, Kei Fujita, Tetsuji Morishita, Yotaro Ochi, Shigeru Chiba, Nana Sasaki, Michiko Ichii, Kazunori Imada, Mizuki Watanabe, Masakatsu Hishizawa, Yasuko Miyahara, Yoshitomo Maesako, Yasuhiro Tanaka, Satoko Oka, Masaaki Tsuji, Satoshi Yoshihara, Kinuko Mitani, Yasunori Ueda, Toshiyuki Kitano, Mitsumasa Watanabe, Nobuo Sezaki, Tadakazu Kondo, Senji Kasahara, Akifumi Takaori-Kondo, Nobuhiro Kanemura, Seishi Ogawa, Yasuhito Nannya","doi":"10.1038/s41375-025-02625-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02625-3","url":null,"abstract":"Venetoclax plus azacitidine (VEN + AZA) is widely used in acute myeloid leukemia (AML). This study explored the role of static and dynamic profiles of mutational clonal burden to predict outcomes by analyzing marrow samples from 228 VEN + AZA treated AML cases at “Pre-treatment” (n = 228), “Best-response” (n = 105), and “Relapse” (n = 27) phases using targeted-capture sequencing. In a multivariate model, older age, prior AZA, TP53 mutation with variant allele frequency ≥0.10, and RAS-pathway mutations predicted shorter overall survival (OS), while BCORL1 mutation predicted longer OS. Notably, myelodysplasia-related gene mutations, which constitute adverse factors in ELN 2022, predicted favorable survival. Achieving composite complete remission (CRc) significantly predicted longer OS (P < 0.001) but showed residual mutations in 76.2% of the cases. Among CRc cases, relapse-free survival was stratified by molecular clearance of mutations other than DNMT3A, ASXL1, and TET2 (P = 0.04). In addition, 37% of relapsed cases showed a change of major clones, with 40% having potential targets of molecular-targeting treatment. This study revealed the novel prognostic role of myelodysplasia-related gene mutations and established the importance of molecular response assessment in CRc phase.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"58 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857362","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

Myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes: a practical guide to diagnosis and management 骨髓增生异常综合征/骨髓增生性肿瘤重叠综合征：诊断和管理的实用指南

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-19 DOI: 10.1038/s41375-025-02620-8

Douglas Tremblay, Robert P. Hasserjian, Raajit K. Rampal

引用次数: 0

GVHD prophylaxis in matched related stem cell transplantation: Why post-transplant cyclophosphamide can be recommended a study by the EBMT transplant complications working party 匹配相关干细胞移植的GVHD预防：为什么移植后环磷酰胺可以推荐EBMT移植并发症工作组的一项研究

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-17 DOI: 10.1038/s41375-025-02619-1

Olaf Penack, Mouad Abouqateb, Christophe Peczynski, William Boreland, Malek Benakli, Nicolaus Kröger, Igor Wolfgang Blau, Didier Blaise, Jaime Sanz, Matthias Eder, Hakan Ozdogu, Dominik Schneidawind, Annoek E. C. Broers, Gerald. G. Wulf, Alberto Mussetti, Ivan Moiseev, Charlotte Graham, Hélène Schoemans, Zinaida Peric

{"title":"GVHD prophylaxis in matched related stem cell transplantation: Why post-transplant cyclophosphamide can be recommended a study by the EBMT transplant complications working party","authors":"Olaf Penack, Mouad Abouqateb, Christophe Peczynski, William Boreland, Malek Benakli, Nicolaus Kröger, Igor Wolfgang Blau, Didier Blaise, Jaime Sanz, Matthias Eder, Hakan Ozdogu, Dominik Schneidawind, Annoek E. C. Broers, Gerald. G. Wulf, Alberto Mussetti, Ivan Moiseev, Charlotte Graham, Hélène Schoemans, Zinaida Peric","doi":"10.1038/s41375-025-02619-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02619-1","url":null,"abstract":"Rabbit anti-thymocyte globulin (rATG) reduced chronic GVHD after matched related donor (MRD) allogeneic stem cell transplantation (alloSCT) from 69% to 32% in a randomized trial and is the recommended standard in Europe. Post-transplantation Cyclophosphamide (PTCy) is an emerging alternative but lacks such solid data in MRD alloSCT. We therefore analyzed outcomes of rATG (n = 4140) vs. PTCy (n = 1069) in adult patients with hematologic malignancies undergoing MRD alloSCT between 2017 and 2021 in the EBMT database. The provided hazard ratios (HR) and P-values are adjusted for potential risk factors using multivariate analysis. Results are given at 2 years after alloSCT for all endpoints except for acute GVHD (100 days). The main difference was a lower relapse incidence after PTCy vs. rATG (26.2% vs. 32.8%; HR 0.78 [CI 95%: 0.66–0.92], p = 0.003). Interaction analyses confirmed the consistency of this result across different disease risk index and conditioning intensity subgroups. Other major transplant outcomes showed no significant differences: non-relapse mortality, overall survival, progression-free survival, GVHD-free relapse-free survival, incidence and severity of acute GVHD as well as chronic GVHD. In summary, PTCy results in comparable GVHD and survival outcomes but lower relapse rates compared to rATG. We conclude that PTCy can be recommended in MRD alloSCT.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"266 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847089","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

T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments t细胞急性淋巴细胞白血病：亚型流行，临床结果，和新兴的靶向治疗

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-17 DOI: 10.1038/s41375-025-02599-2

Maxim Buckley, David T. Yeung, Deborah L. White, Laura N. Eadie

{"title":"T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments","authors":"Maxim Buckley, David T. Yeung, Deborah L. White, Laura N. Eadie","doi":"10.1038/s41375-025-02599-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02599-2","url":null,"abstract":"T-cell Acute Lymphoblastic Leukaemia (T-ALL) is a high-risk hematological disease constituting ~20% of acute leukemias. To date, the only subtype recognized by the World Health Organization’s International Consensus Classification is early T-cell precursor ALL. To improve clinical outcomes, several studies have investigated and defined T-ALL genomic subtypes within cohorts of varied ages and geographical locations. These studies have also utilized differing analysis methods including whole transcriptome, exome, or genome sequencing as well as immunophenotyping and cytogenetic testing. As a result, there are significant differences in reported subtypes as well as the frequency at which each occurs. The reported clinical outcomes for specific genomic alterations also depend on patient demographics and treatment protocols. This review synthesizes the data from four T-ALL genomic landscape studies establishing consensus and highlighting differences, details clinical outcomes for the most common genomic alterations observed in T-ALL patients, and proposes novel avenues for future investigation and treatment.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"108 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841342","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

An oncolytic adenovirus targeting SLAMF7 demonstrates anti-myeloma efficacy 一种靶向SLAMF7的溶瘤腺病毒显示出抗骨髓瘤的功效

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-17 DOI: 10.1038/s41375-025-02617-3

Georgia Stewart, Simon Tazzyman, Yidan Sun, Rebecca E. Andrews, Jack Harrison, Darren Lath, Jenny Down, Georgia Robinson, Xue Wang, Munitta Muthana, Andrew. D. Chantry, Michelle A. Lawson

{"title":"An oncolytic adenovirus targeting SLAMF7 demonstrates anti-myeloma efficacy","authors":"Georgia Stewart, Simon Tazzyman, Yidan Sun, Rebecca E. Andrews, Jack Harrison, Darren Lath, Jenny Down, Georgia Robinson, Xue Wang, Munitta Muthana, Andrew. D. Chantry, Michelle A. Lawson","doi":"10.1038/s41375-025-02617-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02617-3","url":null,"abstract":"We investigated a novel SLAMF7-promoter driven oncolytic adenovirus (Ad[CE1A]) as a potential therapeutic for multiple myeloma, an incurable hematological malignancy. Ad[CE1A] infection, replication, and oncolysis were assessed in a panel of myeloma cell lines (n = 8) and ex vivo samples from myeloma patients (n = 17) and healthy donors (HDs) (n = 14). Ad[CE1A] efficiently infected, replicated, and induced oncolysis in myeloma cells, but not in control cell lines or HDs, demonstrating selective cytotoxicity. Mechanistic studies revealed Ad[CE1A]-induced cell death is caspase-independent, with a potential involvement of necroptosis. Ad[CE1A] also altered immunogenic cell death markers (calreticulin, CD47, extracellular ATP), enhanced antigen presentation via increased MHC class I and II receptor expression (HLA-ABC and HLA-DR), and stimulated bystander cytokine killing, indicating potential for direct and immune-mediated anti-myeloma responses. In vivo experiments with 5TGM1 syngeneic and U266 xenograft models showed Ad[CE1A] significantly reduced myeloma tumor burden compared to vehicle control. Combination therapy with anti-myeloma drugs, bortezomib, melphalan, panobinostat and pomalidomide, enhanced Ad[CE1A] efficacy, with melphalan upregulating SLAMF7, resulting in increased viral replication. In summary, these findings support Ad[CE1A] as a promising myeloma therapy.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"9 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847094","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