Blood最新文献_第9页

Acute myeloid leukemia with RUNX1::CBFA2T3 fusion.

IF 21 1区医学

Blood Pub Date : 2025-03-13 DOI: 10.1182/blood.2024027698

Wei J Wang, Sanam Loghavi

引用次数: 0

Low counts count after CAR-T for ALL.

IF 21 1区医学

Blood Pub Date : 2025-03-13 DOI: 10.1182/blood.2024027489

Regina M Myers, Michael A Pulsipher

引用次数: 0

Single-cell epigenetic and clonal analysis decodes disease progression in pediatric acute myeloid leukemia. 单细胞表观遗传和克隆分析解码儿童急性髓性白血病的疾病进展。

IF 21 1区医学

Blood Pub Date : 2025-03-13 DOI: 10.1182/blood.2024025618

Boyu Cui, Lanlan Ai, Minghui Lei, Yongjuan Duan, Chao Tang, Jingliao Zhang, Yan Gao, Xuan Li, Caiying Zhu, Yingchi Zhang, Xiaofan Zhu, Tomoya Isobe, Wenyu Yang, Berthold Göttgens, Ping Zhu

{"title":"Single-cell epigenetic and clonal analysis decodes disease progression in pediatric acute myeloid leukemia.","authors":"Boyu Cui, Lanlan Ai, Minghui Lei, Yongjuan Duan, Chao Tang, Jingliao Zhang, Yan Gao, Xuan Li, Caiying Zhu, Yingchi Zhang, Xiaofan Zhu, Tomoya Isobe, Wenyu Yang, Berthold Göttgens, Ping Zhu","doi":"10.1182/blood.2024025618","DOIUrl":"10.1182/blood.2024025618","url":null,"abstract":"Abstract: Pediatric acute myeloid leukemia (pAML) is a clonal disease with recurrent genetic alterations that affect epigenetic states. However, the implications of epigenetic dysregulation in disease progression remain unclear. Here, we interrogated single-cell and clonal level chromatin accessibility of bone marrow samples from 28 patients with pAML representing multiple subtypes using mitochondrial single-cell assay for transposase-accessible chromatin with sequencing, which revealed distinct differentiation hierarchies and abnormal chromatin accessibility in a subtype-specific manner. Innate immune signaling was commonly enhanced across subtypes and related to improved advantage of clonal competition and unfavorable prognosis, with further reinforcement in a relapse-associated leukemia stem cell-like population. We identified a panel of 31 innate immunity-related genes to improve the risk classification of patients with pAML. By comparing paired diagnosis and postchemotherapy relapse samples, we showed that primitive cells significantly reduced major histocompatibility complex class II signaling, suggesting an immune evasion mechanism to facilitate their expansion at relapse. Key regulators orchestrating cell cycle dysregulation were identified to contribute to pAML relapse in drug-resistant clones. Our work establishes the single-cell chromatin accessibility landscape at clonal resolution and reveals the critical involvement of epigenetic disruption, offering insights into classification and targeted therapies of patients with pAML.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1211-1224"},"PeriodicalIF":21.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811846","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

Antiaging for Ph-like ALL: targeting senescence.

IF 21 1区医学

Blood Pub Date : 2025-03-13 DOI: 10.1182/blood.2024027815

Ilaria Iacobucci

引用次数: 0

The chromatin accessibility landscape of pediatric AML.

IF 21 1区医学

Blood Pub Date : 2025-03-13 DOI: 10.1182/blood.2024027585

Ambre M Giguelay, Leif S Ludwig

引用次数: 0

Large-scale dependency and drug screens characterize the therapeutic vulnerabilities of Multiple Myeloma with 1q.

IF 21 1区医学

Blood Pub Date : 2025-03-12 DOI: 10.1182/blood.2024025102

Romanos Sklavenitis-Pistofidis, Elizabeth D Lightbody, Mairead Reidy, Junko Tsuji, Jean-Baptiste Alberge, Michelle P Aranha, Daniel Lewis Heilpern-Mallory, Harvey G Roweth, Daisy Huyng, Stephen Jun Fei Chong, Anna Y Chung, Jeremy Zhang, Liam Hackett, Nicholas J Haradhvala, Ting Wu, Nang Kham Su, Brianna Berrios, Saveliy Belkin, Ankit K Dutta, Ryan A Knudson, Carolyn Brandt, Patricia T Greipp, Matthew S Davids, Maria Papaioannou, Gad Getz, Irene M Ghobrial, Salomon Manier

{"title":"Large-scale dependency and drug screens characterize the therapeutic vulnerabilities of Multiple Myeloma with 1q.","authors":"Romanos Sklavenitis-Pistofidis, Elizabeth D Lightbody, Mairead Reidy, Junko Tsuji, Jean-Baptiste Alberge, Michelle P Aranha, Daniel Lewis Heilpern-Mallory, Harvey G Roweth, Daisy Huyng, Stephen Jun Fei Chong, Anna Y Chung, Jeremy Zhang, Liam Hackett, Nicholas J Haradhvala, Ting Wu, Nang Kham Su, Brianna Berrios, Saveliy Belkin, Ankit K Dutta, Ryan A Knudson, Carolyn Brandt, Patricia T Greipp, Matthew S Davids, Maria Papaioannou, Gad Getz, Irene M Ghobrial, Salomon Manier","doi":"10.1182/blood.2024025102","DOIUrl":"https://doi.org/10.1182/blood.2024025102","url":null,"abstract":"The development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for MM patients with 1q+ stands to benefit a large portion of patients in need of more effective management. Here, we employed large-scale dependency screens and drug screens to systematically characterize the therapeutic vulnerabilities of MM with 1q+ and displayed increased sensitivity to MCL1 and PI3K inhibitors. Using single-cell RNA sequencing, we compared subclones with and without 1q+ within the same patient tumors and demonstrated that 1q+ is associated with higher levels of MCL1 and the PI3K pathway. Furthermore, by isolating isogenic clones with different copy number profiles for part of the chromosome 1q arm, we observed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain. Lastly, we demonstrated synergy between MCL1 and PI3K inhibitors and dissected their mechanism of action in MM with 1q+, uncovering a cytostatic effect. In conclusion, this study highlights that MM with 1q+ may present enhanced sensitivity to MCL1 and PI3K inhibitors, enabling their use at lower doses without sacrificing efficacy, and may thus accelerate the development of targeted therapy for patients with MM and 1q+.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613209","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

Efficacy of Combined CD38 and PD1 Inhibition with Isatuximab and Cemiplimab for Relapsed/Refractory NK/T-Cell Lymphoma.

IF 21 1区医学

Blood Pub Date : 2025-03-12 DOI: 10.1182/blood.2024027109

Seok Jin Kim, Jing Quan Lim, Sang Eun Yoon, Deok-Hwan Yang, Ji Hyun Lee, Sung Yong Oh, Yoon Seok Choi, Seong Hyun Jeong, Min Kyoung Kim, Sung-Nam Lim, Junhun Cho, Bon Park, Kyung Ju Ryu, Seunghyun Choi, Yoon Park, Kerry May Huifen Lim, Nur Ayuni Binte Muhammad Taib, Choon Kiat Ong, Soon Thye Lim, Won Seog Kim

{"title":"Efficacy of Combined CD38 and PD1 Inhibition with Isatuximab and Cemiplimab for Relapsed/Refractory NK/T-Cell Lymphoma.","authors":"Seok Jin Kim, Jing Quan Lim, Sang Eun Yoon, Deok-Hwan Yang, Ji Hyun Lee, Sung Yong Oh, Yoon Seok Choi, Seong Hyun Jeong, Min Kyoung Kim, Sung-Nam Lim, Junhun Cho, Bon Park, Kyung Ju Ryu, Seunghyun Choi, Yoon Park, Kerry May Huifen Lim, Nur Ayuni Binte Muhammad Taib, Choon Kiat Ong, Soon Thye Lim, Won Seog Kim","doi":"10.1182/blood.2024027109","DOIUrl":"https://doi.org/10.1182/blood.2024027109","url":null,"abstract":"This study aimed to assess the efficacy and safety of combining cemiplimab, an anti-PD1 antibody, with isatuximab, an anti-CD38 antibody, in relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL). The hypothesis was that CD38 blockade could enhance the antitumor activity of PD1 inhibitors. Eligible patients received cemiplimab (250 mg on days 1 and 15) and isatuximab (10 mg/kg on days 2 and 16) intravenously every four weeks for six cycles. Responders then received cemiplimab (350 mg) and isatuximab (10 mg/kg) every three weeks for up to 24 months. The primary endpoint was the complete response (CR) rate based on the best response. Out of 37 patients enrolled, the CR rate was 51% (19/37), exceeding the primary endpoint of 40%, and the objective response rate was 65% (24/37). After a median follow-up of 30.2 months (95% CI: 25.6-34.8 months), the median progression-free survival was 9.5 months (95% CI: 1.4-17.6 months), while the median overall survival had not yet been reached. Patients achieving CR received a median of 28 cycles (range: 4-33), and the median duration of response for responders (n = 24) was 29.4 months (95% CI: 15.4-43.4 months). Structural variations disrupting the 3'-UTR of PD-L1 and high PD-L1 expression were observed in responders. Most adverse events were mild (grade 1-2), with grade ≥3 events (32%) and no treatment-related deaths. The combination of isatuximab and cemiplimab demonstrated sustained antitumor activity and a manageable safety profile in R/R ENKTL. This phase II trial is registered at www.clinicaltrials.gov as #NCT04763616.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613293","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

A Controlled Trial for Preventing Priapism in Sickle Cell Anemia: Hydroxyurea plus Placebo vs Hydroxyurea plus Tadalafil.

IF 21 1区医学

Blood Pub Date : 2025-03-12 DOI: 10.1182/blood.2024027898

Ibrahim Musa Idris, Aminu Abba Yusuf, Ismail Isah Ismail, Awwal Musa Borodo, Mustapha Shuaibu Hikima, Shehu Abubakar Kana, Tukur Aliyu, Kabiru Musan Gedu, Atiku Usman Jibrillah, Sani Ali Aji, Aisha Kuliya-Gwarzo, Kabeer Bello Mohammed, Jamil A Galadanci, Rukayya Sunusi Alkassim, Mohammad Abba Suwaid, Nafiu Hussaini, Mark Rodeghier, Arthur Louis Burnett, Michael R DeBaun

{"title":"A Controlled Trial for Preventing Priapism in Sickle Cell Anemia: Hydroxyurea plus Placebo vs Hydroxyurea plus Tadalafil.","authors":"Ibrahim Musa Idris, Aminu Abba Yusuf, Ismail Isah Ismail, Awwal Musa Borodo, Mustapha Shuaibu Hikima, Shehu Abubakar Kana, Tukur Aliyu, Kabiru Musan Gedu, Atiku Usman Jibrillah, Sani Ali Aji, Aisha Kuliya-Gwarzo, Kabeer Bello Mohammed, Jamil A Galadanci, Rukayya Sunusi Alkassim, Mohammad Abba Suwaid, Nafiu Hussaini, Mark Rodeghier, Arthur Louis Burnett, Michael R DeBaun","doi":"10.1182/blood.2024027898","DOIUrl":"https://doi.org/10.1182/blood.2024027898","url":null,"abstract":"Recurrent ischemic priapism is a common complication of sickle cell anemia (SCA) and is associated with devastating physical and psychosocial consequences. All previous trials for priapism prevention have failed to demonstrate clear efficacy. We conducted a randomized, controlled, double-blind phase 2 feasibility trial comparing fixed moderate-dose hydroxyurea plus placebo (usual care arm) versus fixed moderate-dose hydroxyurea plus tadalafil (experimental arm) in 64 men (18- 40 years) with at least three episodes of SCA-related priapism in the past 12 months. Priapism data were obtained via daily text messages to the participants. The trial's primary outcome measures were 100% recruitment, 98.4% retention, and 93.5% adherence rates. Over a median of 10 months (IQR: 3-12), 2.5 and 3.02 priapism events per participant-month were recorded in the usual care and the experimental arms, with an incidence rate ratio of 0.8; 95% CI: 0.3 -1.9; p= 0.654. Serious adverse events (p=0.999) and hospitalizations (p=0.289) were similar in both arms. Sperm concentration, motility, and normal morphology significantly decreased on hydroxyurea therapy but recovered to pre-hydroxyurea levels three months after therapy cessation. Post-hoc, single-arm, pre- and post-analysis comparing the priapism rate in the treatment phase to pre-randomization showed a 58.3% priapism incidence rate reduction in the usual care arm (5.9 to 2.5 events per month; difference 3.4, 95% CI: 1.1 - 5.8; p=0.005]) and 66.3% priapism reduction in the experimental arm (8.9 to 3.02 events per month; difference 5.9; 95% CI: 3.4 - 8.5; p<0.001]). A randomized controlled trial for priapism prevention is feasible in men with SCA. (NCT05142254).","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613285","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

101(8)3126 Hu (Lichtenstein) retraction.

IF 21 1区医学

Blood Pub Date : 2025-03-12 DOI: 10.1182/blood.2025029190

Production Staff

引用次数: 0

Clonal Hematopoiesis Landscape in Frequent Blood Donors.

IF 21 1区医学

Blood Pub Date : 2025-03-11 DOI: 10.1182/blood.2024027999

Darja Karpova, Hector Huerga Encabo, Elisa Donato, Silvia Calderazzo, Michael Scherer, Miriam Llorian-Sopena, Aino-Maija Leppä, Roberto Würth, Patrick Stelmach, Despoina Papazoglou, Alessandra Ferrelli, Steven Ngo, Iuliia Kotova, Sabine Harenkamp, Kai Zimmer, Dominik Wolf, Jasper Panten, John Reed, Adriana Przybylla, Torsten Tonn, Annette Kopp-Schneider, Lars Velten, John F DiPersio, Terrence N Wong, Dominique Bonnet, Halvard Bonig, Andreas Trumpp

{"title":"Clonal Hematopoiesis Landscape in Frequent Blood Donors.","authors":"Darja Karpova, Hector Huerga Encabo, Elisa Donato, Silvia Calderazzo, Michael Scherer, Miriam Llorian-Sopena, Aino-Maija Leppä, Roberto Würth, Patrick Stelmach, Despoina Papazoglou, Alessandra Ferrelli, Steven Ngo, Iuliia Kotova, Sabine Harenkamp, Kai Zimmer, Dominik Wolf, Jasper Panten, John Reed, Adriana Przybylla, Torsten Tonn, Annette Kopp-Schneider, Lars Velten, John F DiPersio, Terrence N Wong, Dominique Bonnet, Halvard Bonig, Andreas Trumpp","doi":"10.1182/blood.2024027999","DOIUrl":"10.1182/blood.2024027999","url":null,"abstract":"Donor blood saves lives, yet the potential impact of recurrent large-volume phlebotomy on donor health and hematopoietic stem cells (HSCs) remains largely unexplored. In our study, we conducted a comprehensive screening of 217 older male volunteer donors with a history of extensive blood donation (>100 life-time donations) to investigate the phenomenon of clonal hematopoiesis (CH). No significant difference in the overall incidence of CH was found in frequent donors (FD) compared to sporadic donors (<10 life-time donations, 212 donors). However, upon deeper analysis of mutations in DNMT3A, the most commonly affected gene in CH, we observed distinct mutational patterns between the FD and age/sex matched control donor (CD) cohorts. Functional analysis of FD enriched DNMT3A variants examined in CRISPR-edited human HSCs demonstrated their competitive outgrowth potential upon stimulation with erythropoietin (EPO), a hormone which increases in response to blood loss. In contrast, clones harboring leukemogenic DNMT3A R882 mutations increase upon stimulation with IFNy. Through concurrent mutational and immunophenotypic profiling of primary samples at single cell resolution, a myeloid bias of premalignant R882 mutant HSCs was found, while no significant lineage bias was observed in HSCs harboring EPO responsive DNMT3A variants. The latter exhibited preferential erythroid differentiation when persistent erythropoietic stress was applied to CRISPR-edited human HSC xenografts. Our data demonstrate a nuanced ongoing Darwinian evolution at the somatic stem cell level, with EPO identified as a novel environmental factor that favors HSCs carrying certain DNMT3A mutations.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603791","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