Leukemia最新文献_第2页

Correspondence to “A novel lncRNA SNHG29 regulates EP300-related histone acetylation modification and inhibits FLT3-ITD AML development” 对应于“一种新的lncRNA SNHG29调节ep300相关组蛋白乙酰化修饰并抑制FLT3-ITD AML发展”

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-20 DOI: 10.1038/s41375-025-02643-1

Xiaoyang Wang, Hang Yao, Jiaohao Chen, Xiaogu Liu

{"title":"Correspondence to “A novel lncRNA SNHG29 regulates EP300-related histone acetylation modification and inhibits FLT3-ITD AML development”","authors":"Xiaoyang Wang, Hang Yao, Jiaohao Chen, Xiaogu Liu","doi":"10.1038/s41375-025-02643-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02643-1","url":null,"abstract":"We read the article “A novel lncRNA SNHG29 regulates EP300-related histone acetylation modification and inhibits FLT3-ITD AML development” by Liu Shan et al. with great interest [1]. The study identified the role of the novel lncRNA SNHG29 in FLT3-ITD acute myeloid leukemia (AML), demonstrating that it suppresses AML progression by binding to and regulating the histone acetyltransferase EP300, thereby influencing histone acetylation modifications and the expression of key AML-related genes. The research team has provided new potential therapeutic targets and research directions for AML treatment, and their findings hold significant implications for developing novel therapeutic strategies against AML.The article makes an important contribution to the field of AML research, but we note a number of issues that may affect reader understanding and the reproducibility of experimental results. First, in the results section titled “SNHG29 is associated with proliferation and drug sensitivity of FLT3-ITD AML cells”, the authors report that “Overexpressed SNHG29 significantly inhibited proliferation and colony formation of MV4-11 and MOLM-13 cells, manifested by CCK-8 and clone formation (Fig. 3C) results.” However, the colony-forming assay lacks critical experimental parameters that may affect the reproducibility of the experiments. We recommend that the authors provide essential methodological details (e.g., agar concentration, culture conditions, and colony-counting criteria [2, 3]) and include representative colony images for both the OV-NC and OV-SNHG29 groups to enhance the rigor of the data [4, 5].","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"11 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097169","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

Trajectories from single-cells to PAX5-driven leukemia reveal PAX5-MYC interplay in vivo 从单细胞到pax5驱动的白血病的轨迹揭示了PAX5-MYC在体内的相互作用

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-20 DOI: 10.1038/s41375-025-02626-2

Franziska Auer, Mina N. F. Morcos, Mikko Sipola, Irfan Akhtar, Sanni Moisio, Julia Vogt, Rebecca Haag, Mari Lahnalampi, Tiina J. Tuononen, Andrea Hanel, Anna Viitasalo, Ulrike A. Friedrich, Andreas Dahl, Carolin Prexler, Aleksandra A. Pandyra, Polina Stepensky, Masatoshi Takagi, Arndt Borkhardt, Merja Heinäniemi, Julia Hauer

{"title":"Trajectories from single-cells to PAX5-driven leukemia reveal PAX5-MYC interplay in vivo","authors":"Franziska Auer, Mina N. F. Morcos, Mikko Sipola, Irfan Akhtar, Sanni Moisio, Julia Vogt, Rebecca Haag, Mari Lahnalampi, Tiina J. Tuononen, Andrea Hanel, Anna Viitasalo, Ulrike A. Friedrich, Andreas Dahl, Carolin Prexler, Aleksandra A. Pandyra, Polina Stepensky, Masatoshi Takagi, Arndt Borkhardt, Merja Heinäniemi, Julia Hauer","doi":"10.1038/s41375-025-02626-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02626-2","url":null,"abstract":"PAX5 acts as a master regulator of B-cell proliferation and differentiation. Its germline and somatic deregulation have both been implicated in the development of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the process how reduced PAX5 transcriptional activity mediates progression to BCP-ALL, is still poorly understood. Here, we characterized the longitudinal effects of PAX5 reduction on healthy, pre-leukemic and BCP-ALL cells at the single-cell level. Cell-surface marker analysis revealed a genotype-driven enrichment of the pre-BII population in healthy Pax5± mice. This population showed downregulated B-cell receptor signaling, while DNA replication/repair and cell-cycle signaling pathways were upregulated. Moreover, we observed a shift in the kappa/lambda light chain ratio toward lambda rearranged B-cells. Transplantation experiments further validated a delay of Pax5± pre-BII cells in maturation and transition to IgM-positivity. Additionally, single-cell RNA-Sequencing and bulk ATAC-Sequencing of different stages of BCP-ALL evolution showed that Pax5± pre-leukemic cells lose their B-cell identity and display Myc activation. Subsequently, BCP-ALLs acquired additional RAG-mediated aberrations and driver mutations in JAK-STAT and RAS-signaling pathways. Together, this study elucidates molecular and functional checkpoints in PAX5-mediated pre-leukemic cell progression exploitable for therapeutic intervention and demonstrates that PAX5 reduction is sufficient to initiate clonal evolution to BCP-ALL through activation of MYC.<figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"18 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097170","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

The evolving landscape of epigenetic target molecules and therapies in myeloid cancers: focus on acute myeloid leukemia and myeloproliferative neoplasms. 表观遗传靶点分子和治疗在骨髓癌中的演变景观：集中于急性髓性白血病和骨髓增生性肿瘤。

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-15 DOI: 10.1038/s41375-025-02639-x

Michael W M Kühn,Naveen Pemmaraju,Florian H Heidel

{"title":"The evolving landscape of epigenetic target molecules and therapies in myeloid cancers: focus on acute myeloid leukemia and myeloproliferative neoplasms.","authors":"Michael W M Kühn,Naveen Pemmaraju,Florian H Heidel","doi":"10.1038/s41375-025-02639-x","DOIUrl":"https://doi.org/10.1038/s41375-025-02639-x","url":null,"abstract":"Research on myeloid neoplasms, a field that has been driving scientific advances in cancer for over 50 years, has yielded many discoveries that have fundamentally reshaped our understanding of cancer biology. These insights, often the product of leukemia research, have been instrumental in developing more mechanism-based treatments in the early 2000s [1]. Recognizing epigenetic dysregulation as a common disease mechanism in myeloid cancers has been groundbreaking regarding recent treatment developments that exploit chromatin-based oncogenic mechanisms. In the case of acute myeloid leukemia (AML), sequencing studies aimed at assessing the complement of genetic alterations demonstrated that more than 60% of AML cases harbored disease-driving mutations in epigenetic regulators. This high prevalence underscores the importance of epigenetic dysregulation in AML pathogenesis [2, 3]. Chromatin regulators commonly control disease-specific transcriptional programs, making them attractive therapeutic targets to manipulate neoplastic gene expression programs, particularly in myeloid neoplasms. Several drugs targeting epigenetic mechanisms and exploiting myeloid disease-specific dependencies have recently been approved for treating myeloid neoplasms. Many additional drugs are currently being investigated in clinical trials, and numerous new compound developments are being studied in preclinical studies. This manuscript will review (1) chromatin-based disease mechanisms, such as DNA methylation, chromatin regulatory complexes, and histone modifications, currently investigated for therapeutic exploitation in myeloid malignancies, and (2) therapeutic developments already approved or investigated for treating these diseases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"15 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065833","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: Preclinical discovery and initial clinical data of WVT078, a BCMA × CD3 bispecific antibody. 更正：BCMA × CD3双特异性抗体WVT078的临床前发现和初步临床数据。

IF 12.8 1区医学

Leukemia Pub Date : 2025-05-15 DOI: 10.1038/s41375-025-02516-7

Marc S Raab, Yael C Cohen, Fredrik Schjesvold, Kimberly Aardalen, Adwait Oka, Andrew Spencer, Martin Wermke, Anita D Souza, Jonathan L Kaufman, Anna Maria Cafro, Enrique M Ocio, Noriko Doki, Kristin Henson, Gina Trabucco, Ana Carrion, Florent C Bender, Pierre-Eric Juif, Adonai Fessehatsion, Liqiong Fan, Jeffrey P Stonehouse, John W Blankenship, Brian Granda, Serena De Vita, Haihui Lu

引用次数: 0

Refining histopathological growth pattern-based risk group discrimination in nodular lymphocyte-predominant Hodgkin lymphoma: an analysis from the German Hodgkin Study Group 在结节淋巴细胞为主的霍奇金淋巴瘤中，细化基于组织病理学生长模式的风险群体区分：来自德国霍奇金研究组的分析

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-13 DOI: 10.1038/s41375-025-02641-3

Dennis A. Eichenauer, Aylin Basaran, Ina Bühnen, Michael Fuchs, Bastian von Tresckow, Andreas Rosenwald, Martin-Leo Hansmann, Heinz-Wolfram Bernd, Peter Borchmann, Wolfram Klapper, Sylvia Hartmann

{"title":"Refining histopathological growth pattern-based risk group discrimination in nodular lymphocyte-predominant Hodgkin lymphoma: an analysis from the German Hodgkin Study Group","authors":"Dennis A. Eichenauer, Aylin Basaran, Ina Bühnen, Michael Fuchs, Bastian von Tresckow, Andreas Rosenwald, Martin-Leo Hansmann, Heinz-Wolfram Bernd, Peter Borchmann, Wolfram Klapper, Sylvia Hartmann","doi":"10.1038/s41375-025-02641-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02641-3","url":null,"abstract":"Histopathological growth patterns (GP) in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have previously been divided into GP AB (typical) vs CDEF (variant). However, it is unclear whether this division is optimal. We thus investigated alternative GP grouping approaches (GP ABC vs DEF; GP ABCF vs DE). Overall, 583 NLPHL patients who had first-line treatment within GHSG trials were included in the analysis. Median age was 39 years; 74% of patients were male; 76% presented with early-stage and 24% with advanced-stage disease. The 5-year and 10-year progression-free survival (PFS) estimates for all patients were 85.9% and 76.6%; overall survival (OS) estimates were 95.8% and 94.5%. Significant PFS and OS differences were detected for the comparison GP ABCF vs DE with worse outcomes for the GP DE group (HR: 1.7; 95%-CI: 1.1–2.7; HR: 2.5; 95%-CI: 1.1–5.7). No PFS and OS differences were observed for the comparisons GP AB vs CDEF and GP ABC vs DEF. Median time to death was shorter and death more often due to NLPHL in the GP DE (13 months; 66.7%) than in the GP ABCF (31 months; 5.6%) group. Hence, the division of GP into GP ABCF vs DE allows an optimized GP-based risk group discrimination in NLPHL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"113 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940625","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

Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia 儿童b细胞前体急性淋巴细胞白血病中IKZF1基因组改变的异质性和复发风险

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-13 DOI: 10.1038/s41375-025-02633-3

Ruth W. Wang’ondu, Emily Ashcraft, Ti-Cheng Chang, Kathryn G. Roberts, Samuel W. Brady, Yiping Fan, William Evans, Mary V. Relling, Kristine R. Crews, Jun Yang, Wenjian Yang, Stanley Pounds, Gang Wu, Meenakshi Devidas, Kelly Maloney, Leonard Mattano, Reuven J. Schore, Anne Angiolillo, Eric Larsen, Wanda Salzer, Michael J. Burke, Mignon L. Loh, Sima Jeha, Ching-Hon Pui, Hiroto Inaba, Cheng Cheng, Charles G. Mullighan

{"title":"Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia","authors":"Ruth W. Wang’ondu, Emily Ashcraft, Ti-Cheng Chang, Kathryn G. Roberts, Samuel W. Brady, Yiping Fan, William Evans, Mary V. Relling, Kristine R. Crews, Jun Yang, Wenjian Yang, Stanley Pounds, Gang Wu, Meenakshi Devidas, Kelly Maloney, Leonard Mattano, Reuven J. Schore, Anne Angiolillo, Eric Larsen, Wanda Salzer, Michael J. Burke, Mignon L. Loh, Sima Jeha, Ching-Hon Pui, Hiroto Inaba, Cheng Cheng, Charles G. Mullighan","doi":"10.1038/s41375-025-02633-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02633-3","url":null,"abstract":"Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-progenitor acute lymphoblastic leukemia (B-ALL). The relationship between the type of IKZF1 alteration, B-ALL genomic subtype and outcome are incompletely understood. B-ALL subtype and genomic alterations were determined using transcriptome and genomic sequencing, and SNP microarray analysis in 688 pediatric patients with B-ALL in the St. Jude Total Therapy XV and 16 studies. IKZF1 alterations were identified in 115 (16.7%) patients, most commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%). These alterations were associated with 5-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). In separate multivariable analyses adjusting for genetic subtype groups and other factors, IKZF1 deletions of exons 4–7 (P = 0.0002), genomic IKZF1plus with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adverse prognostic factors. Associations of genomic IKZF1plus and exon 4–7 deletions with adverse outcomes were confirmed in an independent cohort. The type of IKZF1 alteration, together with the subtype, are informative for risk stratification and to predict response in patients with B-ALL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"74 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940663","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

Acute myeloid leukemia stem cells remodel the bone marrow niche via TGF-β-activated Alcam+ bone lining cells, creating a self-sustaining environment 急性髓系白血病干细胞通过TGF-β激活的Alcam+骨衬细胞重塑骨髓生态位，创造自我维持的环境

IF 11.4 1区医学

Leukemia Pub Date : 2025-05-13 DOI: 10.1038/s41375-025-02640-4

Ngan Thi Kim Nguyen, Hisayuki Yao, Kentaro Hosokawa, Yuki Esaki, Ryosuke Yuta, Shunichi Adachi, Fumio Arai

{"title":"Acute myeloid leukemia stem cells remodel the bone marrow niche via TGF-β-activated Alcam+ bone lining cells, creating a self-sustaining environment","authors":"Ngan Thi Kim Nguyen, Hisayuki Yao, Kentaro Hosokawa, Yuki Esaki, Ryosuke Yuta, Shunichi Adachi, Fumio Arai","doi":"10.1038/s41375-025-02640-4","DOIUrl":"https://doi.org/10.1038/s41375-025-02640-4","url":null,"abstract":"TO THE EDITOR:Relapse after achieving complete remission remains a critical challenge in the treatment of acute myeloid leukemia (AML). One of the reasons for relapse is the presence of leukemia stem cells (LSCs) [1]. LSCs are a subset of leukemia cells that possess self-renewal capabilities like normal stem cells, and they can divide to produce more LSCs and leukemia cells [2]. Like normal hematopoietic stem cells (HSCs), LSCs reside in specialized bone marrow (BM) microenvironments, termed niches, that regulate their function through complex signaling networks [3]. These niches are classified into the vascular niche in the central BM and the endosteal niche at the bone surface. The vascular niche surrounds the BM vasculature and includes mesenchymal stromal cells (MSCs), endothelial cells, and non-myelinating Schwann cells [4]. The endosteal niche at the internal bone surface consists of bone lining cells (BLCs) [5]. BLCs can be further subdivided into Alcam+ Sca-1− cells (Alcam+ BLCs), Alcam− Sca-1+ cells (Sca-1+ BLCs), and Alcam− Sca-1− cells. Sca-1+ BLCs are considered to be MSCs, whereas Alcam+ BLCs are a heterogeneous group composed mainly of osteoblasts expressing high levels of osteoblastic markers [5]. By considering the periphery of the endosteum of the BM as the endosteal niche and the central region of the BM as the vascular niche, we performed analyses to clarify the properties and characteristics of LSCs in each niche and the relationship between LSCs and each niche. Clarifying the molecular mechanisms of niche support for LSCs should provide a new perspective for the development of leukemia treatments.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"29 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940626","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

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