Leukemia最新文献_第6页

Is there really an accelerated phase of chronic myeloid leukaemia at presentation? 慢性髓性白血病在发病时真的有加速期吗？

IF 12.8 1区医学

Leukemia Pub Date : 2024-12-04 DOI: 10.1038/s41375-024-02486-2

Sen Yang, Xiaoshuai Zhang, Robert Peter Gale, Xiaojun Huang, Qian Jiang

{"title":"Is there really an accelerated phase of chronic myeloid leukaemia at presentation?","authors":"Sen Yang, Xiaoshuai Zhang, Robert Peter Gale, Xiaojun Huang, Qian Jiang","doi":"10.1038/s41375-024-02486-2","DOIUrl":"10.1038/s41375-024-02486-2","url":null,"abstract":"Whether there is really a distinct accelerated phase (AP) at diagnosis in chronic myeloid leukaemia (CML) in the context of tyrosine kinase-inhibitor (TKI)-therapy is controversial. We studied 2122 consecutive subjects in chronic phase (CP, n = 1837) or AP (n = 285) at diagnosis classified according to the 2020 European LeukemiaNet (ELN) classification. AP subjects with increased basophils only had similar transformation-free survival (TFS) and survival compared with CP subjects classified as ELTS intermediate-risk. Those with increased blasts only had worse TFS but similar survival compared with CP subjects classified as ELTS high-risk. AP subjects with decreased platelets only had similar TFS but worse survival compared with subjects classified as ELTS high-risk. Proportions of CP and AP subjects meeting the 2020 ELN TKI-response milestones were similar. However, worse TFS at 3-month and survival at 6- or 12-month were only in AP subjects failing to meet ELN milestones. Findings were similar using the 2022 International Consensus Classification (ICC) criteria for AP replacing decreased platelets with additional cytogenetic abnormalities. Our data support the 2022 WHO classification of CML eliminating AP. We suggest adding a very high-risk cohort to the ELTS score including people with increased blasts or decreased platelets and dividing CML into 2 phases at diagnosis: CP and acute or blast phases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"391-399"},"PeriodicalIF":12.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02486-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia HMX3是mecom阴性KMT2A::MLLT3急性髓单细胞白血病的一个关键易感性

IF 12.8 1区医学

Leukemia Pub Date : 2024-12-04 DOI: 10.1038/s41375-024-02485-3

Saioa Arza-Apalategi, Branco M. H. Heuts, Saskia M. Bergevoet, Roos Meering, Daan Gilissen, Pascal W. T. C. Jansen, Anja Krippner-Heidenreich, Peter J. M. Valk, Michiel Vermeulen, Olaf Heidenreich, Torsten Haferlach, Joop H. Jansen, Joost H. A. Martens, Bert A. van der Reijden

{"title":"HMX3 is a critical vulnerability in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia","authors":"Saioa Arza-Apalategi, Branco M. H. Heuts, Saskia M. Bergevoet, Roos Meering, Daan Gilissen, Pascal W. T. C. Jansen, Anja Krippner-Heidenreich, Peter J. M. Valk, Michiel Vermeulen, Olaf Heidenreich, Torsten Haferlach, Joop H. Jansen, Joost H. A. Martens, Bert A. van der Reijden","doi":"10.1038/s41375-024-02485-3","DOIUrl":"10.1038/s41375-024-02485-3","url":null,"abstract":"KMT2A::MLLT3 acute myelomonocytic leukemia (AML) comes in two clinically and biologically different subtypes. One is characterized by inferior outcome, older age, and MECOM oncogene expression. The other is mainly observed in children and young adults, associates with better clinical outcome, but lacks MECOM. To identify cell fate determining transcription factors downstream of KMT2A::MLLT3, we applied a bioinformatic algorithm that integrates gene and enhancer expression from primary MECOM-positive and -negative KMT2A::MLLT3 AML samples. This identified MECOM to be most influential in the MECOM-positive group, while neuronal transcription factor HMX3 was most influential in the MECOM-negative group. In large AML cohorts, HMX3 expression associated with a unique gene expression profile, younger age (p < 0.002) and KMT2A-rearranged and KAT6A-CREBBP leukemia (p < 0.00001). HMX3 was not expressed in other major genetic risk groups and healthy blood cells. RNA-sequencing analyses following forced HMX3 expression in healthy CD34+ cells and its silencing in KMT2A::MLT3 cells showed that HMX3 drives cancer-associated E2F and MYC gene programs (p < 0.001). HMX3 expression in healthy CD34+ cells blocked monocytic but not granulocytic colony formation. Strikingly, HMX3 silencing in KMT2A::MLLT3 patient cells resulted in cell cycle arrest, monocytic differentiation and apoptosis. Thus, the neuronal transcription factor HMX3 is a leukemia-specific vulnerability in KMT2A::MLLT3 AML.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"371-380"},"PeriodicalIF":12.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763191","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

Correction: Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia 纠正：在一项4年随访的ELEVATE-TN研究中，比较阿卡拉布替尼加或不加obinutuzumab与obinutuzumab加氯霉素治疗treatment-naïve慢性淋巴细胞白血病的疗效和安全性。

IF 12.8 1区医学

Leukemia Pub Date : 2024-12-03 DOI: 10.1038/s41375-024-02487-1

Jeff P. Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, John M. Pagel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Gillian Corbett, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, Steven Coutre, George Follows, Patricia Walker, Karin Karlsson, Paolo Ghia, Ann Janssens, Florence Cymbalista, Jennifer A. Woyach, Emmanuelle Ferrant, William G. Wierda, Veerendra Munugalavadla, Ting Yu, Min Hui Wang, John C. Byrd

引用次数: 0

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-28 DOI: 10.1038/s41375-024-02481-7

Jiacheng Lou, Yi Zhang, Jingfen Tao, Wen Jin, Yongmei Zhu, Zhuo Wang, Min Wu, Hongmei Yi, Xiaoxiao Chen, Shuhong Shen, Junmin Li, Zhu Chen, Saijuan Chen, Yangyang Xie, Li Chen, Kankan Wang

引用次数: 0

Spatial transcriptomic approaches for characterising the bone marrow landscape: pitfalls and potential 表征骨髓景观的空间转录组学方法：陷阱和潜力。

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-28 DOI: 10.1038/s41375-024-02480-8

Rosalin A. Cooper, Emily Thomas, Anna M. Sozanska, Carlo Pescia, Daniel J. Royston

引用次数: 0

Relevance of blast counts for genetic subclassification in MDS 爆炸计数与 MDS 基因亚分类的相关性

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-27 DOI: 10.1038/s41375-024-02484-4

Sandra Huber, Torsten Haferlach, Stephan Hutter, Gregor Hoermann, Wolfgang Kern, Claudia Haferlach

引用次数: 0

Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma 全面的基因组分析揭示了小儿ALK阳性非典型大细胞淋巴瘤的分子异质性

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-26 DOI: 10.1038/s41375-024-02468-4

Timothy I. Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C. Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S. Lim, Vasiliki Leventaki

{"title":"Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma","authors":"Timothy I. Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C. Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S. Lim, Vasiliki Leventaki","doi":"10.1038/s41375-024-02468-4","DOIUrl":"10.1038/s41375-024-02468-4","url":null,"abstract":"Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10–15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription (JUNB), and epigenetic regulators (TET1, KMT2B, KMT2A, KMT2C, KMT2E). Gene expression and methylation profiling consistently subclassified ALK+ ALCLs into two groups characterized by differential ALK expression levels. The ALK-low group showed enrichment of pathways associated with immune response, cytokine signaling, and a hypermethylated predominant pattern compared to the ALK-high group, which had more frequent copy number changes and was enriched with pathways associated with cell growth, proliferation, and metabolism. Altogether, these findings suggest that there is molecular heterogeneity within pediatric ALK+ ALCL, predicting distinct biological mechanisms that may provide novel insights into disease pathogenesis and represent prognostic markers.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"199-210"},"PeriodicalIF":12.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718403","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

High CD44 expression and enhanced E-selectin binding identified as biomarkers of chemoresistant leukemic cells in human T-ALL CD44高表达和E-选择素结合增强被确定为人类T-ALL化疗耐受性白血病细胞的生物标志物

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-24 DOI: 10.1038/s41375-024-02473-7

Julien Calvo, Irina Naguibneva, Anthony Kypraios, Florian Gilain, Benjamin Uzan, Baptiste Gaillard, Lea Bellenger, Laurent Renou, Christophe Antoniewski, Helene Lapillonne, Arnaud Petit, Paola Ballerini, Stéphane JC. Mancini, Tony Marchand, Jean-François Peyron, Françoise Pflumio

{"title":"High CD44 expression and enhanced E-selectin binding identified as biomarkers of chemoresistant leukemic cells in human T-ALL","authors":"Julien Calvo, Irina Naguibneva, Anthony Kypraios, Florian Gilain, Benjamin Uzan, Baptiste Gaillard, Lea Bellenger, Laurent Renou, Christophe Antoniewski, Helene Lapillonne, Arnaud Petit, Paola Ballerini, Stéphane JC. Mancini, Tony Marchand, Jean-François Peyron, Françoise Pflumio","doi":"10.1038/s41375-024-02473-7","DOIUrl":"10.1038/s41375-024-02473-7","url":null,"abstract":"T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy characterized by increased proliferation and incomplete maturation of T-cell progenitors, for which relapse is often of poor prognosis. To improve patient outcomes, it is critical to understand the chemoresistance mechanisms arising from cell plasticity induced by the bone marrow (BM) microenvironment. Single-cell RNA sequencing of human T-ALL cells from adipocyte-rich and adipocyte-poor BM revealed a distinct leukemic cell population defined by quiescence and high CD44 expression (Ki67neg/lowCD44high). During in vivo treatment, these cells evaded chemotherapy, and were further called Chemotherapy-resistant Leukemic Cells (CLCs). Patient sample analysis revealed Ki67neg/lowCD44high CLCs at diagnosis and during relapse, with each displaying a specific transcriptomic signature. Interestingly, CD44high expression in T-ALL Ki67neg/low CLCs was associated with E-selectin binding. Analysis of 39 human T-ALL samples revealed significantly enhanced E-selectin binding activity in relapse/refractory samples compared with drug-sensitive samples. These characteristics of chemoresistant T-ALL CLCs provide key insights for prognostic stratification and novel therapeutic options.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"323-336"},"PeriodicalIF":12.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02473-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dimethyl fumarate ameliorates chronic graft-versus-host disease by inhibiting Tfh differentiation via Nrf2 富马酸二甲酯通过Nrf2抑制Tfh分化，从而改善慢性移植物抗宿主疾病

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-23 DOI: 10.1038/s41375-024-02475-5

Fulian Lyu, Huanle Gong, Xiaojin Wu, Xin Liu, Yinghao Lu, Xiya Wei, Chenchen Liu, Yaoyao Shen, Yuhang Wang, Lei Lei, Jia Chen, Shoubao Ma, Hongjian Sun, Di Yu, JingJing Han, Yang Xu, Depei Wu

{"title":"Dimethyl fumarate ameliorates chronic graft-versus-host disease by inhibiting Tfh differentiation via Nrf2","authors":"Fulian Lyu, Huanle Gong, Xiaojin Wu, Xin Liu, Yinghao Lu, Xiya Wei, Chenchen Liu, Yaoyao Shen, Yuhang Wang, Lei Lei, Jia Chen, Shoubao Ma, Hongjian Sun, Di Yu, JingJing Han, Yang Xu, Depei Wu","doi":"10.1038/s41375-024-02475-5","DOIUrl":"10.1038/s41375-024-02475-5","url":null,"abstract":"Chronic graft-versus-host disease (cGVHD), characterized by chronic tissue inflammation and fibrosis involving multiple organs, remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Dimethyl fumarate (DMF) is an anti-inflammatory drug approved for the treatment of multiple sclerosis and psoriasis. We previously reported that DMF effectively inhibits acute GVHD (aGVHD) while preserving the graft-versus-leukemia effect. However, the role of DMF in cGVHD progression remains unknown. Here, we found that DMF administration significantly suppresses follicular helper T cell (Tfh) differentiation, and germinal center formation and alleviates disease severity in different murine cGVHD models. Mechanistically, DMF treatment downregulates IL-21 transcription by activation of Nrf2, thus orchestrating Tfh-related gene programs both in mice and humans. The inhibitory role of DMF on Tfh cell differentiation was diminished in Nrf2 deficient T cells. Importantly, the therapeutic potential of DMF in clinical cGVHD has been validated in human data whereby DMF effectively reduces IL-21 production and Tfh cell generation in peripheral blood mononuclear cells from active cGVHD patients and further attenuates xenograft GVHD. Collectively, our findings reveal that DMF potently inhibits cGVHD development by repressing Tfh cell differentiation via Nrf2, paving the way for the treatment of cGVHD in the clinic.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"473-481"},"PeriodicalIF":12.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690643","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

miR-196b-Oct1/2 axis regulates DNMT3A-mutant AML pathogenesis miR-196b-Oct1/2 轴调控 DNMT3A 突变型急性髓细胞性白血病的发病机制

IF 12.8 1区医学

Leukemia Pub Date : 2024-11-23 DOI: 10.1038/s41375-024-02456-8

Michael E. Lawler, Melanie L. Goetz, Jennifer S. Romer-Seibert, Holly A. Gamlen, Edwina McGlinn, Sara E. Meyer

引用次数: 0