Leukemia最新文献_第9页

Professor LU Daopei: Chinese Transplant Pioneer, 30 October, 1931-2 April, 2025. 陆道培教授：中国器官移植先驱，1931年10月30日—2025年4月。

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-09 DOI: 10.1038/s41375-025-02636-0

Robert Peter Gale

引用次数: 0

Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements 新诊断急性髓系白血病伴KMT2A重排的特点及预后

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-09 DOI: 10.1038/s41375-025-02634-2

Alex Bataller, Hannah E. Goulart, Ghayas C. Issa, Courtney D. DiNardo, Naval Daver, Tapan Kadia, Alexandre Bazinet, Ian M. Bouligny, Jayastu Senapati, Fadi G. Haddad, Gautam Borthakur, Koji Sasaki, Nicholas J. Short, Musa Yilmaz, Guillermo Montalban-Bravo, Guiling Tang, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Elias Jabbour

{"title":"Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements","authors":"Alex Bataller, Hannah E. Goulart, Ghayas C. Issa, Courtney D. DiNardo, Naval Daver, Tapan Kadia, Alexandre Bazinet, Ian M. Bouligny, Jayastu Senapati, Fadi G. Haddad, Gautam Borthakur, Koji Sasaki, Nicholas J. Short, Musa Yilmaz, Guillermo Montalban-Bravo, Guiling Tang, Sanam Loghavi, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Elias Jabbour","doi":"10.1038/s41375-025-02634-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02634-2","url":null,"abstract":"Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A. Signaling-related genes (NRAS 30%, KRAS 23% and FLT3-TKD 16%) were the most frequently mutated in patients with KMT2Ar AML. Patients treated with intensive chemotherapy (IT) achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 81%, and when combined with venetoclax, the CR/CRi rate increased to 100%. Patients treated with low intensity treatment (LIT) achieved an CR/CRi rate of 33%, and when combined with venetoclax, the CR/CRi rate was 61%. For patients treated with IT, the 5-year overall survival (OS) and event-free survival (EFS) rates were 66% and 64%, respectively, compared with 7% in those treated with LIT. Thirty-nine patients (57%) underwent allogeneic stem cell transplantation after achieving CR/CRi. For patients treated with LIT, multivariate analysis demonstrated that N/KRAS mutations were predictive for OS (HR 2.93, 95% CI 1.18–7.29, P = 0.021) and EFS (HR 3.51, 95% CI 1.35–9.24, P = 0.01). In summary, outcomes in KMT2Ar AML have improved over years in patients treated with IT, whereas those treated with LIT continue to show poor survival, highlighting the need for novel combinations.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"49 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930934","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

Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia SETD1B催化结构域对mll重排白血病中H3K4me3宽度和MYC表达的调控

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-08 DOI: 10.1038/s41375-025-02638-y

Shintaro Izumi, Ko Ohtani, Makoto Matsumoto, Seito Shibata, Bahityar Rahmutulla, Masaki Fukuyo, Mitsutaka Nishimoto, Hideo Miyagawa, Emiko Sakaida, Koutaro Yokote, Issay Kitabayashi, Kimi Araki, Atsushi Kaneda, Takayuki Hoshii

{"title":"Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia","authors":"Shintaro Izumi, Ko Ohtani, Makoto Matsumoto, Seito Shibata, Bahityar Rahmutulla, Masaki Fukuyo, Mitsutaka Nishimoto, Hideo Miyagawa, Emiko Sakaida, Koutaro Yokote, Issay Kitabayashi, Kimi Araki, Atsushi Kaneda, Takayuki Hoshii","doi":"10.1038/s41375-025-02638-y","DOIUrl":"https://doi.org/10.1038/s41375-025-02638-y","url":null,"abstract":"Histone H3 lysine 4 trimethylation (H3K4me3) is abundant in mixed-lineage leukemia-rearranged (MLL-r) acute myeloid leukemia (AML) cells; however, the responsible enzymes and their roles remain unclear. This study aimed to identify the modifier responsible for high H3K4me3 modification in MLL-r leukemia and its downstream targets essential for the cell proliferation. Here, we performed a CRISPR-tiling screen against known H3K4 methylation modifiers in an MLL-r AML model. Disrupting the SETD1B catalytic SET domain caused depletion of FLT3-ITD or NrasG12D-expressing AML cells, and gene expression downregulation, particularly in the MYC pathway. SETD1B SET domain loss results in a significant decrease in H3K4me3 breadth. Exogenous MYC expression or disrupting H3K4 demethylase KDM5C significantly restored growth defects in SETD1B SET domain-mutant cells. These data indicated that SETD1B was required for H3K4me3 breadth and MYC expression. Thus, a thorough understanding of SETD1B-mediated H3K4me3 breadth is critical for developing markers and therapies for MYC-dependent leukemia subtypes.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"35 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920168","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 neoplasms with ring sideroblasts without SF3B1 mutations in adults: enrichment of germline variants in congenital sideroblastic anemia genes 成人无SF3B1突变的环形铁母细胞骨髓增生异常肿瘤：先天性铁母细胞贫血基因的种系变异富集

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-07 DOI: 10.1038/s41375-025-02629-z

Sandra Novoa-Jáuregui, Sandra Huber, Maria Gabarrós-Subirà, Tzu Hua Chen-Liang, Sara Torres-Esquius, Salvador Carrillo-Tornel, Marta Santiago, Teresa Bernal del Castillo, Iván Martín-Castillo, Francisca Maria Hernandez, Mónica del Rey, Alessandro Liquori, Mar Tormo, Jose Cervera, Francesc Bosch, David Valcárcel, Claudia Haferlach, María Díez-Campelo, María Julia Montoro, Torsten Haferlach, Andrés Jerez

{"title":"Myelodysplastic neoplasms with ring sideroblasts without SF3B1 mutations in adults: enrichment of germline variants in congenital sideroblastic anemia genes","authors":"Sandra Novoa-Jáuregui, Sandra Huber, Maria Gabarrós-Subirà, Tzu Hua Chen-Liang, Sara Torres-Esquius, Salvador Carrillo-Tornel, Marta Santiago, Teresa Bernal del Castillo, Iván Martín-Castillo, Francisca Maria Hernandez, Mónica del Rey, Alessandro Liquori, Mar Tormo, Jose Cervera, Francesc Bosch, David Valcárcel, Claudia Haferlach, María Díez-Campelo, María Julia Montoro, Torsten Haferlach, Andrés Jerez","doi":"10.1038/s41375-025-02629-z","DOIUrl":"https://doi.org/10.1038/s41375-025-02629-z","url":null,"abstract":"Ring sideroblasts (RS) are erythroid precursors with pathological, iron-laden mitochondria, exposed by Prussian blue staining as a perinuclear ring of blue granules [1]. RS can be seen in non-clonal (toxic or metabolic) and clonal disorders (congenital sideroblastic anemias and acquired myeloid neoplasms) [2]. Myelodysplastic neoplasms (MDS) account for the majority of RS cases, and their presence has been a defining feature of MDS in the World Health Organization (WHO) classification since 2002 [3]. In 2011, a high proportion of MDS-RS patients were found to be somatically mutated in SF3B1 [4]. However, approximately 20% of cases lack the SF3B1 mutation (SF3B1wt MDS-RS) without clear evidence regarding the molecular driver event [5,6,7].On the other hand, congenital forms of sideroblastic anemia (CSA) are uncommon, with variable inheritance patterns and causative genes involved in heme biosynthesis [2]. They are diagnosed usually within the first two decades of life. Nevertheless, a “second hit”, such as acquired skewed X-chromosome inactivation, can lead to diagnoses in mid to late adulthood in women carrying mutations in the erythroid-specific isoform of aminolevulinic acid synthase 2 (ALAS2), causing the most common CSA, the X-linked sideroblastic anemia (XLSA). These cases encompass one-quarter of clinically affected XLSA probands and have led to what have been considered SF3B1wt MDS-RS misdiagnoses [8,9,10].","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916001","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

Predisposition to hematopoietic malignancies by deleterious germline CHEK2 variants 有害种系CHEK2变异对造血恶性肿瘤的易感性

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-07 DOI: 10.1038/s41375-025-02635-1

Ryan J. Stubbins, Stephen Arnovitz, Jennie Vagher, Anase Asom, Melody Perpich, Madeline Pies, Imo J. Akpan, Edward Chew, Joshua Bridgers, Aly Karsan, Courtnee Rodgers, Ashwin Koppayi, Hatice Basdag, Michael W. Drazer, Soma Das, Jason Cheng, Afaf E. G. Osman, Lucy A. Godley

{"title":"Predisposition to hematopoietic malignancies by deleterious germline CHEK2 variants","authors":"Ryan J. Stubbins, Stephen Arnovitz, Jennie Vagher, Anase Asom, Melody Perpich, Madeline Pies, Imo J. Akpan, Edward Chew, Joshua Bridgers, Aly Karsan, Courtnee Rodgers, Ashwin Koppayi, Hatice Basdag, Michael W. Drazer, Soma Das, Jason Cheng, Afaf E. G. Osman, Lucy A. Godley","doi":"10.1038/s41375-025-02635-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02635-1","url":null,"abstract":"The role of germline CHEK2 variants in hematopoietic malignancies (HMs) is poorly understood. We examined pathogenic/likely pathogenic (P/LP) CHEK2 variants in patients with hereditary HMs (HHMs), a solid tumor risk cohort, public datasets, and a knock-in mouse model. In the HHM cohort, 57 probands had germline P/LP CHEK2 variants, mostly p.I157T (53%, 30/57). Among CHEK2 p.I157T carriers, 43% (19/44) had myeloid malignancies, 32% (14/44) had lymphoid malignancies, and 2% (1/44) had both. Among those with other germline P/LP CHEK2 alleles, 36% (13/36) had myeloid malignancies, 28% (10/36) had lymphoid malignancies, and 6% (2/36) had both. CHEK2 p.I157T was enriched in HM patients (OR 6.44, 95%CI 3.68–10.73, P < 0.001). In a solid tumor risk cohort, 36% (15/42) of CHEK2 p.I157T patients had a HM family history. A genome wide association study showed enrichment of CHEK2 loss-of-function variants with myeloid leukemia (P = 5.78e−7). In public acute myeloid leukemia (AML) datasets, 1% (16/1348) of patients had P/LP CHEK2 variants. In a public myelodysplastic neoplasms (MDS) dataset, 2% (5/214) had P/LP CHEK2 variants. Chek2 p.I161T mice, homologous to human p.I157T, had worse survival as heterozygotes (P = 0.037) or homozygotes (P = 0.005), with fewer Lin-CD34+ and Lin-cKit+ cells. Our data suggest P/LP CHEK2 variants are HHM risk alleles.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"103 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916002","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

TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma TP53和CDKN2A的改变定义了淋巴结T滤泡辅助细胞淋巴瘤患者预后不良的亚组

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-02 DOI: 10.1038/s41375-025-02631-5

Yuta Ito, Joji Shimono, Keisuke Kawamoto, Kanako C. Hatanaka, Yasunori Kogure, Mariko Tabata, Yuki Saito, Kota Mizuno, Sara Horie, Yosuke Mizukami, Junji Koya, Koichi Murakami, Takanori Teshima, Yutaka Hatanaka, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Hiroaki Miyoshi, Yoshihiro Matsuno, Koichi Ohshima, Keisuke Kataoka, Masao Nakagawa

{"title":"TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma","authors":"Yuta Ito, Joji Shimono, Keisuke Kawamoto, Kanako C. Hatanaka, Yasunori Kogure, Mariko Tabata, Yuki Saito, Kota Mizuno, Sara Horie, Yosuke Mizukami, Junji Koya, Koichi Murakami, Takanori Teshima, Yutaka Hatanaka, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Hiroaki Miyoshi, Yoshihiro Matsuno, Koichi Ohshima, Keisuke Kataoka, Masao Nakagawa","doi":"10.1038/s41375-025-02631-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02631-5","url":null,"abstract":"Nodal T follicular helper cell lymphoma (nTFHL) exhibits unique immunophenotypes and somatic alterations, while the prognostic value of these alterations remains unclear. By analyzing 173 nTFHL cases, we identified 36 driver genes, including 4 novel ones (TET3, HLA-C, NRAS, and KLF2). Then, we classified nTFHL cases into four molecular subgroups by major driver alterations. TR-I (+) and TR-I (−) were characterized by TET2 and/or RHOA mutations with and without IDH2 mutations; AC53 by TP53 and/or CDKN2A alterations and aneuploidy; and NSD with no subgroup-defining alterations (namely without any of the above alterations). AC53 exhibited the worst survival, while NSD, particularly those lacking driver alterations, showed the best prognosis. nTFHL had a better prognosis than peripheral T-cell lymphoma, not otherwise specified, when TP53 and/or CDKN2A alterations were absent. Multivariable analyses showed that AC53, the presence of driver alterations, and international prognostic index high-risk were independently associated with worse survival. Finally, we developed a simple prognostic index (mTFHL-PI), which classified patients into three risk categories with a median OS of 181, 67, and 20 months, respectively. Our study identifies novel prognostic factors, namely TP53 and/or CDKN2A alterations and the presence of driver alterations, demonstrating the clinical relevance of molecular classification in nTFHL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898076","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: Proteomic screening identifies PF4/Cxcl4 as a critical driver of myelofibrosis. 更正：蛋白质组学筛选确定PF4/Cxcl4是骨髓纤维化的关键驱动因素。

IF 12.8 1区医学

Leukemia Pub Date : 2025-05-01 DOI: 10.1038/s41375-025-02587-6

Daniele Capitanio, Francesca R Calledda, Vittorio Abbonante, Daniele Cattaneo, Manuela Moriggi, Niccolò Bartalucci, Cristina Bucelli, Delfina Tosi, Umberto Gianelli, Alessandro Maria Vannucchi, Alessandra Iurlo, Cecilia Gelfi, Alessandra Balduini, Alessandro Malara

引用次数: 0

Correction: Regulatory T cells promote the stemness of leukemia stem cells through IL10 cytokine-related signaling pathway. 更正：调节性T细胞通过IL10细胞因子相关信号通路促进白血病干细胞的干细胞性。

IF 12.8 1区医学

Leukemia Pub Date : 2025-05-01 DOI: 10.1038/s41375-025-02618-2

Yingxi Xu, Junli Mou, Ying Wang, Wei Zhou, Qing Rao, Haiyan Xing, Zheng Tian, Kejing Tang, Min Wang, Jianxiang Wang

引用次数: 0

Correction: Correlation of progression-free survival and overall survival after treatment for relapsed Hodgkin lymphoma: individual patient data analysis of randomized German Hodgkin Study Group (GHSG) Trials. 修正：复发霍奇金淋巴瘤治疗后无进展生存期和总生存期的相关性：随机德国霍奇金研究组（GHSG）试验的个体患者数据分析。

IF 12.8 1区医学

Leukemia Pub Date : 2025-05-01 DOI: 10.1038/s41375-025-02597-4

P J Bröckelmann, H Müller, M Fuchs, S Gillessen, D A Eichenauer, S Borchmann, A S Robertz, K Behringer, J Welters, J Ferdinandus, B Böll, H Tharmaseelan, X Yang, C Kobe, H T Eich, C Baues, W Klapper, P Borchmann, B von Tresckow

引用次数: 0

Is the bone marrow microenvironment the hidden catalyst in malignant haematopoiesis? 骨髓微环境是恶性造血的隐性催化剂吗？

IF 11.4 1区医学

Leukemia Pub Date : 2025-04-29 DOI: 10.1038/s41375-025-02630-6

Syed A. Mian, Steven Ngo, Dominique Bonnet

引用次数: 0