Leukemia最新文献_第3页

Spatial transcriptomic approaches for characterising the bone marrow landscape: pitfalls and potential.

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 11.4 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 11.4 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":"https://doi.org/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":"36 1","pages":""},"PeriodicalIF":11.4,"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 11.4 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":"https://doi.org/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.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"104 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 11.4 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":"https://doi.org/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":"15 1","pages":""},"PeriodicalIF":11.4,"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 11.4 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

Dimethyl fumarate and extracorporeal photopheresis combination-therapy synergize in inducing specific cell death and long-term remission in cutaneous T cell lymphoma 富马酸二甲酯和体外射频联合疗法在诱导特异性细胞死亡和皮肤T细胞淋巴瘤长期缓解方面具有协同作用

IF 11.4 1区医学

Leukemia Pub Date : 2024-11-23 DOI: 10.1038/s41375-024-02479-1

Özge Ç. Şener, Susanne Melchers, Luisa Tengler, Paul L. Beltzig, Jana D. Albrecht, Deniz Tümen, Karsten Gülow, Jochen S. Utikal, Sergij Goerdt, Tobias Hein, Jan P. Nicolay

{"title":"Dimethyl fumarate and extracorporeal photopheresis combination-therapy synergize in inducing specific cell death and long-term remission in cutaneous T cell lymphoma","authors":"Özge Ç. Şener, Susanne Melchers, Luisa Tengler, Paul L. Beltzig, Jana D. Albrecht, Deniz Tümen, Karsten Gülow, Jochen S. Utikal, Sergij Goerdt, Tobias Hein, Jan P. Nicolay","doi":"10.1038/s41375-024-02479-1","DOIUrl":"https://doi.org/10.1038/s41375-024-02479-1","url":null,"abstract":"Primary cutaneous T cell lymphomas (CTCL) are characterized by high relapse rates to initially highly effective therapies. Combination therapies have proven beneficial, particularly if they incorporate extracorporeal photopheresis (ECP). The NF-κB inhibitor dimethyl fumarate (DMF) has proven a new, effective drug in CTCL in a clinical phase II study. In vitro experiments with patient-derived SS cells and the CTCL cell lines HH, HuT 78, and SeAx revealed a synergistic effect of DMF and ECP on cell death induction in CTCL cells. Furthermore, an additional increase in the capacity to inhibit NF-κB in CTCL was detected for the combination treatment compared to DMF monotherapy. The same synergistic effects could be measured for ROS production via decreased Thioredoxin reductase activity and glutathione levels. Consequently, a cell death inhibitor screen indicated that the DMF/ECP combination treatment induces a variety of cell death mechanisms in CTCL. As a first step into clinical translation, 4 patients were already treated with the DMF/ECP combination therapy with an overall response rate of 100% and a time to next treatment in skin and blood of up to 57 months. Therefore, our study introduces the combination treatment of DMF and ECP as a highly effective and long-lasting CTCL therapy.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"12 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694109","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

CLL crosstalk with naïve T cells enhances the differentiation of IL-22-producing T cells and CLL -cell survival CLL 与天真 T 细胞的串联可促进产生 IL-22 的 T 细胞的分化和 CLL 细胞的存活

IF 11.4 1区医学

Leukemia Pub Date : 2024-11-22 DOI: 10.1038/s41375-024-02463-9

Gerardo Ferrer, Florencia Palacios, Pui Yan Chiu, Kelly Wong, Alberto Bueno-Costa, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Shih-Shih Chen, Barbara Sherry, Nicholas Chiorazzi

引用次数: 0

Rheumatoid arthritis and the risk of hematologic malignancies: a nationwide cohort study 类风湿性关节炎与罹患血液系统恶性肿瘤的风险：一项全国性队列研究

IF 11.4 1区医学

Leukemia Pub Date : 2024-11-22 DOI: 10.1038/s41375-024-02477-3

In Young Cho, Kyungdo Han, Jin Hyung Jung, Mi Hee Cho, Dagyeong Lee, Keun Hye Jeon, Dong Wook Shin

引用次数: 0

A DNA methylation database of human and mouse hematological malignancy cell lines 人类和小鼠血液恶性肿瘤细胞系 DNA 甲基化数据库

IF 11.4 1区医学

Leukemia Pub Date : 2024-11-22 DOI: 10.1038/s41375-024-02478-2

Aleix Noguera-Castells, Carlos A. García-Prieto, Gerardo Ferrer, Veronica Davalos, Fernando Setien, Eulàlia Genescà, Jordi Ribera, Josep M. Ribera, Manel Esteller

引用次数: 0