Leukemia最新文献

{"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":"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":"39 2","pages":"438-450"},"PeriodicalIF":12.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02479-1.pdf","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLL crosstalk with naïve T cells enhances the differentiation of IL-22-producing T cells and CLL -cell survival","authors":"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","doi":"10.1038/s41375-024-02463-9","DOIUrl":"10.1038/s41375-024-02463-9","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"499-502"},"PeriodicalIF":12.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02463-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684395","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}

{"title":"Rheumatoid arthritis and the risk of hematologic malignancies: a nationwide cohort study","authors":"In Young Cho, Kyungdo Han, Jin Hyung Jung, Mi Hee Cho, Dagyeong Lee, Keun Hye Jeon, Dong Wook Shin","doi":"10.1038/s41375-024-02477-3","DOIUrl":"https://doi.org/10.1038/s41375-024-02477-3","url":null,"abstract":"<p>The autoimmune and inflammatory pathogenesis of rheumatoid arthritis (RA), the use of immunomodulating therapy, and shared environmental or genetic risk factors between RA and malignancies have raised attention to cancer risk in patients with RA [1], in particular hematologic malignancies [1, 2]. In RA, the presence of autoantibodies is associated with rapid disease progression; however, it is unclear whether seropositivity is associated with hematologic malignancies.</p><p>Moreover, previous studies examining hematologic malignancy risk in patients with RA mostly reported standardized incidence ratios (SIR) [1,2,3,4,5,6], lacking consideration of confounding factors such as smoking, alcohol, and socioeconomic status. Data on Asian populations are also limited, especially regarding leukemia and multiple myeloma (MM). Hematologic malignancies may differ between Western and Asian populations in incidence and pathophysiology according to the type due to genetic and environmental factors; i.e., Hodgkin lymphoma (HL) shows higher incidence rates in Western Europe than East Asia [7].</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"63 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684262","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":"A DNA methylation database of human and mouse hematological malignancy cell lines","authors":"Aleix Noguera-Castells,&nbsp;Carlos A. García-Prieto,&nbsp;Gerardo Ferrer,&nbsp;Veronica Davalos,&nbsp;Fernando Setien,&nbsp;Eulàlia Genescà,&nbsp;Jordi Ribera,&nbsp;Josep M. Ribera,&nbsp;Manel Esteller","doi":"10.1038/s41375-024-02478-2","DOIUrl":"10.1038/s41375-024-02478-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"512-515"},"PeriodicalIF":12.8,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02478-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690647","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}

{"title":"Adding eltrombopag to intensive immunosuppressive therapy for severe aplastic anaemia may help adult patients achieve outcomes similar to paediatric patients","authors":"Bixi Yang,&nbsp;Leyu Wang,&nbsp;Lingling Fu,&nbsp;Miao Chen,&nbsp;Jie Ma,&nbsp;Bing Han","doi":"10.1038/s41375-024-02450-0","DOIUrl":"10.1038/s41375-024-02450-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"261-264"},"PeriodicalIF":12.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678565","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 hematopoiesis in large granular lymphocytic leukemia","authors":"Naomi Kawashima,&nbsp;Carmelo Gurnari,&nbsp;Carlos Bravo-Perez,&nbsp;Yasuo Kubota,&nbsp;Simona Pagliuca,&nbsp;Luca Guarnera,&nbsp;Nakisha D. Williams,&nbsp;Arda Durmaz,&nbsp;Arooj Ahmed,&nbsp;Danai Dima,&nbsp;Fauzia Ullah,&nbsp;Hetty E. Carraway,&nbsp;Abhay Singh,&nbsp;Valeria Visconte,&nbsp;Jaroslaw P. Maciejewski","doi":"10.1038/s41375-024-02460-y","DOIUrl":"10.1038/s41375-024-02460-y","url":null,"abstract":"Past studies described occasional patients with myeloid neoplasms (MN) and coexistent large granular lymphocytic leukemia (LGLL) or T-cell clonopathy of unknown significance (TCUS), which may represent expansion of myeloid clonal hematopoiesis (CH) as triggers or targets of clonal cytotoxic T cell reactions. We retrospectively analyzed 349 LGLL/TCUS patients, 672 MN patients, and 1443 CH individuals to establish the incidence, genetic landscape, and clinical phenotypes of CH in LGLL. We identified 8% of cases overlapping with MN, while CH was found in an additional 19% of cases (CH + /LGLL) of which TET2 (23%) and DNMT3A (14%) were the most common. In MN cohort, 3% of cases showed coexistent LGLL. The incidence of CH in LGLL was exceedingly higher than age-matched CH controls (P &lt; 0.0001). By multivariate analysis, the presence of CH in LGLL (P = 0.026) was an independent risk factor for cytopenia in addition to older&nbsp;age (P = 0.003), splenomegaly (P = 0.015) and STAT3/5B mutations (P = 0.001). CH + /LGLL cases also showed a higher progression rate to MN than CH-/LGLL (10% vs. 2% at 5 years; P = 0.02). A close relationship between CH and LGLL suggests that cytopenia in LGLL may be not only related to LGLL but be also secondary to coexisting clonal cytopenia of unclear significance.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"451-459"},"PeriodicalIF":12.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684396","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":"The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling","authors":"Mahesh Hegde,&nbsp;Mohd H. Ahmad,&nbsp;Roger Mulet Lazaro,&nbsp;Mayumi Sugita,&nbsp;Rui Li,&nbsp;Kai Hu,&nbsp;Claudia Gebhard,&nbsp;Monica L. Guzman,&nbsp;John H. Bushweller,&nbsp;Lihua J. Zhu,&nbsp;Michael Brehm,&nbsp;Scot A. Wolfe,&nbsp;Ruud Delwel,&nbsp;Lucio H. Castilla","doi":"10.1038/s41375-024-02471-9","DOIUrl":"10.1038/s41375-024-02471-9","url":null,"abstract":"Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion oncoprotein&nbsp;CBFβ::MYH11 regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion. Mechanistically, we show that the NRP1 locus has open chromatin in inv(16) AML, and that CBFβ::MYH11 modulates the local function of the transcription factors ERG, GATA2 and RUNX1 to sustain NRP1 levels. We found that ERG activates NRP1 expression, and that CBFβ::MYH11 knockdown represses ERG expression, thereby allowing the repressive activity of GATA2/RUNX1 at three NRP1 enhancers. Functionally, we demonstrate that NRP1 enhances the expansion of leukemic cells in vitro and in mice, and that this activity is dependent on its VEGFR-associated FV/FVIII domain. Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"360-370"},"PeriodicalIF":12.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684427","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":"Global patterns of leukemia by subtype, age, and sex in 185 countries in 2022","authors":"Dagrun S. Daltveit,&nbsp;Eileen Morgan,&nbsp;Murielle Colombet,&nbsp;Eva Steliarova-Foucher,&nbsp;Karima Bendahhou,&nbsp;Rafael Marcos-Gragera,&nbsp;Zheng Rongshou,&nbsp;Alexandra Smith,&nbsp;Hui Wei,&nbsp;Isabelle Soerjomataram","doi":"10.1038/s41375-024-02452-y","DOIUrl":"10.1038/s41375-024-02452-y","url":null,"abstract":"In 2022, leukemia ranked as the second most common hematological malignancy after non-Hodgkin lymphoma worldwide. However, updated global estimates of leukemia incidence by subtype are unavailable. We estimated leukemia incidences for different leukemia subtypes by country, world region, and human developmental index using data from the Cancer Incidence in Five Continents databases combined with the GLOBOCAN 2022 estimates of leukemia in 185 countries. We estimated sex-specific age-standardized rates (ASRs) per 100 000 for children (0–19 years) and adults (20+ years). In adults, the most common leukemia worldwide was AML (males:&nbsp;38%, ASR = 3·1; females:&nbsp;43%, ASR = 2·4), followed by CLL (males:&nbsp;28%, ASR = 2·2; females:&nbsp;24%, ASR = 1·3). In very high HDI countries, the ASR of CLL was higher than the ASR of AML among males (5·2 versus 4·3, respectively) and similar among females (2·9 and 3·0, respectively). In children, the most common leukemia was ALL (boys:&nbsp;70%, ASR = 2·4; girls:&nbsp;68%, ASR = 1·8) followed by AML (boys:&nbsp;22%, ASR = 0·76; girls:&nbsp;25%, ASR = 0·65). ALL proportions varied across world sub-regions from 57&nbsp;to&nbsp;78% among boys, and from 49 to 80% among girls. Our findings suggest clear geographical patterns of leukemia subtypes in adults and children. Further research into underlying causes that explain these variations is needed to support cancer control strategies for prevention and plan national healthcare needs.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"412-419"},"PeriodicalIF":12.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02452-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673884","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}

{"title":"Polycomb group protein Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of self-renewal and proliferation genes","authors":"Wenjie Cai,&nbsp;Xicheng Liu,&nbsp;Sergio Barajas,&nbsp;Shiyu Xiao,&nbsp;Sasidhar Vemula,&nbsp;Hongxia Chen,&nbsp;Yuxia Yang,&nbsp;Christopher Bochers,&nbsp;Danielle Henley,&nbsp;Sheng Liu,&nbsp;Yuzhi Jia,&nbsp;Michelle Hong,&nbsp;Tiffany M. Mays,&nbsp;Maegan L. Capitano,&nbsp;Huiping Liu,&nbsp;Peng Ji,&nbsp;Zhonghua Gao,&nbsp;Diego Pasini,&nbsp;Jun Wan,&nbsp;Feng Yue,&nbsp;Leonidas C. Platanias,&nbsp;Rongwen Xi,&nbsp;Sisi Chen,&nbsp;Yan Liu","doi":"10.1038/s41375-024-02462-w","DOIUrl":"10.1038/s41375-024-02462-w","url":null,"abstract":"Polycomb group (PcG) proteins play important roles in hematopoietic stem cell (HSC) self-renewal. Mel18 and Bmi1 are homologs of the PCGF subunit within the Polycomb repressive complex 1 (PRC1). Bmi1 (PCGF4) enhances HSC self-renewal and promotes terminal differentiation. However, the role of Mel18 (PCGF2) in hematopoiesis is not fully understood and how Mel18 regulates gene transcription in HSCs remains elusive. We found that acute deletion of Mel18 in the hematopoietic compartment significantly increased the frequency of functional HSCs in the bone marrow. Furthermore, we demonstrate that Mel18 inhibits HSC self-renewal and proliferation. RNA-seq studies revealed that HSC self-renewal and proliferation gene signatures are enriched in Mel18−/− hematopoietic stem and progenitors (HSPCs) compared to Mel18+/+ HSPCs. Notably, ATAC-seq revealed increased chromatin accessibility at genes important for HSC self-renewal, whereas CUT&amp;RUN showed decreased enrichment of H2AK119ub1 at genes important for proliferation, leading to increased expression of both Hoxb4 and Cdk4 in Mel18−/− HSPCs. Thus, we demonstrate that Mel18 inhibits hematopoietic stem cell self-renewal through repressing the transcription of genes important for HSC self-renewal and proliferation.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"296-307"},"PeriodicalIF":12.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673902","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":"Graft-versus-host disease after anti-CD19 chimeric antigen receptor T-cell therapy following allogeneic hematopoietic cell transplantation: a transplant complications and paediatric diseases working parties joint EBMT study","authors":"Guillermo Ortí,&nbsp;Christophe Peczynski,&nbsp;William Boreland,&nbsp;Maeve O’Reilly,&nbsp;Malte von Bonin,&nbsp;Adriana Balduzzi,&nbsp;Caroline Besley,&nbsp;Krzysztof Kalwak,&nbsp;Samppa Ryhänen,&nbsp;Tayfun Güngör,&nbsp;Robert F. Wynn,&nbsp;Peter Bader,&nbsp;Stephan Mielke,&nbsp;Didier Blaise,&nbsp;Persis Amrolia,&nbsp;Ibrahim Yakoub-Agha,&nbsp;Friso Calkoen,&nbsp;Maria-Luisa Schubert,&nbsp;Victoria Potter,&nbsp;Herbert Pichler,&nbsp;Nicolaus Kröger,&nbsp;Mi Kwon,&nbsp;Henrik Sengeloev,&nbsp;Anna Torrent,&nbsp;Yves Chalandon,&nbsp;Gwendolyn van Gorkom,&nbsp;Christian Koenecke,&nbsp;Charlotte Graham,&nbsp;Helene Schoemans,&nbsp;Ivan Moiseev,&nbsp;Olaf Penack,&nbsp;Zinaida Peric","doi":"10.1038/s41375-024-02467-5","DOIUrl":"10.1038/s41375-024-02467-5","url":null,"abstract":"In patients diagnosed with B-acute lymphoblastic leukemia (B-ALL) or B-non-Hodgkin’s lymphoma (B-NHL) relapsing after allogeneic stem cell transplantation (allo-HCT), it is a standard practice to perform anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. When collected from the patient after allo-HCT, the produced CAR-T cells are likely to be donor T-cell-derived, creating unknown safety risks due to their potential allo-reactivity. We therefore performed an EBMT registry-based study on the incidence of graft-versus-host disease (GvHD) in this setting. We included 257 allo-HCT patients (n = 172 ≥ 18 years) with B-ALL or B-NHL, treated with anti-CD19 CAR T-cells (tisagenlecleucel n = 184, brexucabtagene autoleucel n = 43 and axicabtagene ciloleucel n = 30), between 2018 and 2022. Three patients developed aGvHD, whereas 6 patients developed cGvHD after CAR T-cell. The 100-day cumulative incidence (CI) of new aGvHD was 1.6% and the 12-month CI of new cGvHD was 2.8%. The 1-year GvHD relapse-free survival and non-relapse mortality were 52.1% and 4.7%, respectively. Last, with a median follow up of 18.8 months, the 1-year overall survival was 76.8%. In summary, the GvHD rate in allo-HCT patients treated with CAR T-cell therapy is relatively low. Our data support the view that GvHD is not a major safety issue in this setting.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 2","pages":"431-437"},"PeriodicalIF":12.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673890","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}