Blood Cancer Discovery最新文献_第4页

Understanding the Molecular Mechanisms Underlying Anemia in Myelodysplastic Syndromes: From Erythropoiesis to New Therapeutic Approaches. 了解骨髓增生异常综合征中贫血的分子机制：从红细胞生成到新的治疗方法。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-25-0393

Vera Adema, Francesco Pesce, Guillermo Garcia-Manero, Valeria Santini, Simona Colla

{"title":"Understanding the Molecular Mechanisms Underlying Anemia in Myelodysplastic Syndromes: From Erythropoiesis to New Therapeutic Approaches.","authors":"Vera Adema, Francesco Pesce, Guillermo Garcia-Manero, Valeria Santini, Simona Colla","doi":"10.1158/2643-3230.BCD-25-0393","DOIUrl":"10.1158/2643-3230.BCD-25-0393","url":null,"abstract":"Minimizing the transfusion burden is one of the primary clinical goals for most patients with myelodysplastic syndromes (MDS), which are incurable hematopoietic stem cell neoplasms. In some patients, supportive red blood cell transfusions can lead to clinical improvement, but frequent transfusions induce iron overload, which can have detrimental effects on cardiac and hepatic function, affect patients' quality of life, and incur additional healthcare costs. In this review, we summarize how erythropoiesis is regulated under steady-state conditions, dissect the molecular mechanisms underlying anemia in MDS, and review therapeutic approaches to overcome ineffective erythropoiesis in patients with these diseases.Significance: A better understanding of the biological mechanisms underlying anemia in MDS is needed to develop targeted therapies for a personalized treatment approach. Anemia, a hallmark of MDS, highly affects patients' quality of life and contributes to overall morbidity. Current knowledge of the mechanisms of action of the available drugs targeting anemia in MDS is limited.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"532-543"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated Analysis of Genomics, Molecular Responses, and Outcomes of CBF-AML with FLAG-Based Therapy on a Phase II Trial. 基于FLAG的CBF-AML 2期临床试验的基因组学、分子反应和结果的综合分析

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-25-0477

Jayastu Senapati, Hagop M Kantarjian, Edward Ayoub, Andres E Quesada, Sanam Loghavi, Koji Sasaki, Tapan M Kadia, Naval Daver, Courtney D DiNardo, Akhil Jain, Mikaela McCabe, Fadi G Haddad, Mark Brandt, Guilin Tang, Yesid Alvarado, Kayla Farish, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Michael Andreeff, Gautam Borthakur

{"title":"Integrated Analysis of Genomics, Molecular Responses, and Outcomes of CBF-AML with FLAG-Based Therapy on a Phase II Trial.","authors":"Jayastu Senapati, Hagop M Kantarjian, Edward Ayoub, Andres E Quesada, Sanam Loghavi, Koji Sasaki, Tapan M Kadia, Naval Daver, Courtney D DiNardo, Akhil Jain, Mikaela McCabe, Fadi G Haddad, Mark Brandt, Guilin Tang, Yesid Alvarado, Kayla Farish, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Michael Andreeff, Gautam Borthakur","doi":"10.1158/2643-3230.BCD-25-0477","DOIUrl":"10.1158/2643-3230.BCD-25-0477","url":null,"abstract":"Fludarabine, cytarabine, and G-CSF-based therapy (FLAG) yields approximately 60% 5-year overall survival (OS) in core-binding factor (CBF) acute myeloid leukemia (AML), with potential added benefit with gemtuzumab ozogamicin (GO). Although measurable residual disease (MRD) status via optimal quantitative polymerase chain reaction (qPCR) response (OPR; qPCR <0.1% at the end of induction and <0.01% during/after consolidation) of fusion transcripts predicts survival, the impact of baseline myeloid mutations on OPR and survival with FLAG remains uncertain. We interrogated these factors in 219 first-line patients with CBF-AML (median age 52 years; range, 19-80) treated on a phase II trial (NCT00801489); 51% received FLAG-GO and 49% FLAG idarubicin. Baseline mutations included 49% kinase pathways (non-MAP kinase), 44% MAP kinase, 11% DNMT3A-ASXL1-TET2, and 7% transcription factors. Five-year relapse-free survival and OS were 67% and 74% overall, respectively, 77% and 80% with FLAG-GO. On multivariate analysis, baseline mutations did not affect OPR or survival, whereas FLAG-GO favored both. In CBF-AML, FLAG-based therapy possibly attenuates the prognostic impact of concurrent baseline genomics.Significance: In CBF-AML treated with conventional intensive chemotherapy, usually 7 + 3, baseline mutations in KIT, chromatin modulators, cohesin complex, etc., garner suboptimal MRD clearance and survival. In our analysis, FLAG-based therapy abrogated the impact of baseline mutations on OPR and survival in CBF-AML, while showing promising long-term survival using FLAG-GO.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"572-585"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147677249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Laying the Foundation for Clinically Actionable Genomic Subtyping in Diffuse Large B-cell Lymphoma. 为弥漫性大b细胞淋巴瘤临床可操作的基因组分型奠定基础。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-25-0327

Margaret A Shipp, Louis M Staudt, Daniel J Hodson, David W Scott, Wei-Li Zhao, Riccardo Dalla-Favera, Ash A Alizadeh, Ryan D Morin

引用次数: 0

MYST Acetyltransferases Interact with SETBP1 and Are a Targetable Therapeutic Vulnerability in SETBP1-Mutant Leukemia. MYST乙酰转移酶与SETBP1相互作用，是SETBP1突变白血病的靶向治疗易感性。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-25-0446

Hanqian L Carlson, Thai T Nguyen, Samantha Tauchmann, Sarah A Carratt, Traci L Kruer, Nana Adjoa Dankyi, Maria E Balasis, Hyeyoon Kim, Chia-Feng Tsai, Tao Liu, Shawn B Shrestha, Jared M Fischer, Eric Padron, Theodore P Braun, Julia E Maxson

{"title":"MYST Acetyltransferases Interact with SETBP1 and Are a Targetable Therapeutic Vulnerability in SETBP1-Mutant Leukemia.","authors":"Hanqian L Carlson, Thai T Nguyen, Samantha Tauchmann, Sarah A Carratt, Traci L Kruer, Nana Adjoa Dankyi, Maria E Balasis, Hyeyoon Kim, Chia-Feng Tsai, Tao Liu, Shawn B Shrestha, Jared M Fischer, Eric Padron, Theodore P Braun, Julia E Maxson","doi":"10.1158/2643-3230.BCD-25-0446","DOIUrl":"10.1158/2643-3230.BCD-25-0446","url":null,"abstract":"Mutations in SETBP1 are associated with adverse prognosis in myeloid malignancies. These mutations stabilize the SETBP1 protein, driving increased expression of a progenitor-associated gene expression program through incompletely described mechanisms. A proteomic screen revealed interactions between SETBP1 and MYST acetyltransferase complexes, including the catalytic subunits-KAT6A and KAT7. In cell line and primary hematopoietic models, mutant SETBP1 increased the localization of MYST complexes at known SETBP1 target genes, including the HOXA cluster, in which they were shown to drive increased histone acetylation and gene expression. Treatment of SETBP1D868N-expressing myeloid progenitors with MYST inhibitors reduced target gene expression. To establish the efficacy of MYST inhibition in vivo, we treated mice harboring a syngeneic SETBP1-mutant leukemia with the clinical-grade MYST inhibitor-PF-9363. This resulted in hematologic control and increased survival. MYST inhibition was also highly effective against a SETBP1-mutant patient-derived xenograft model. These studies identify MYST acetyltransferases as promising therapeutic targets in SETBP1-mutant malignancies.Significance: SETBP1 mutations are markers of high-risk myeloid malignancies, but targeted therapies to improve outcomes in these patient populations are limited. In this study, we identified MYST acetyltransferases as key mediators of mutant SETBP1-driven transcription and showed that MYST inhibitors are highly effective against SETBP1-mutant leukemia models. See related commentary by Soto and Gritsman, p. 506.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"606-623"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rewiring the Leukemic Genome: 3D Chromatin Architecture in B-cell Acute Lymphoblastic Leukemia. 白血病基因组的重新布线：b细胞急性淋巴细胞白血病的三维染色质结构。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-26-0110

Tanja A Gruber

引用次数: 0

Improving Knowledge and Care of Patients with AML: The Need to Get Out of Our Comfort Zone. 提高AML患者的知识和护理：需要走出我们的舒适区

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-26-0053

Ann-Kathrin Eisfeld, Elaine R Mardis

引用次数: 0

Beyond Static Subtypes in Large B-cell Lymphoma: Context, Plasticity, and Therapeutic Logic. 大b细胞淋巴瘤的静态亚型：背景、可塑性和治疗逻辑。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-26-0204

Laura K Hilton, Christopher R Flowers, Jean L Koff

引用次数: 0

New Insights into the Role of Clonotypic B Cells in Plasma-cell Neoplasia. 克隆型B细胞在浆细胞瘤中作用的新认识。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-26-0109

Sungjae Kim, Irene M Ghobrial

引用次数: 0

KATs in the MYST: A New Therapeutic Vulnerability for SETBP1-Mutated Myeloid Malignancies. MYST中的KATs: setbp1突变骨髓恶性肿瘤的新治疗易感性

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-26-0136

Mark Soto, Kira Gritsman

引用次数: 0

3D Chromosome Remodeling in B-cell Development and Acute Lymphoblastic Leukemia. b细胞发育和急性淋巴细胞白血病中的三维染色体重塑。

IF 12.2

Blood Cancer Discovery Pub Date : 2026-07-01 DOI: 10.1158/2643-3230.BCD-25-0315

Yohana E Ghebrechristos, Nikki A Evensen, Romane S Cathelin, Soobeom Lee, Finnegan Clark, Nestor Saiz, Stanley Clarke, Matthew T Witkowski, Ziyan Lin, Sonali Narang, Hua Zhou, Elizabeth Raetz, David T Teachey, Timothée Lionnet, Aristotelis Tsirigos, William L Carroll, Iannis Aifantis

{"title":"3D Chromosome Remodeling in B-cell Development and Acute Lymphoblastic Leukemia.","authors":"Yohana E Ghebrechristos, Nikki A Evensen, Romane S Cathelin, Soobeom Lee, Finnegan Clark, Nestor Saiz, Stanley Clarke, Matthew T Witkowski, Ziyan Lin, Sonali Narang, Hua Zhou, Elizabeth Raetz, David T Teachey, Timothée Lionnet, Aristotelis Tsirigos, William L Carroll, Iannis Aifantis","doi":"10.1158/2643-3230.BCD-25-0315","DOIUrl":"10.1158/2643-3230.BCD-25-0315","url":null,"abstract":"The identification of molecular subgroups of pediatric B-cell acute lymphocytic leukemia (B-ALL) has proven to be a powerful tool in understanding disease pathogenesis and treatment stratification. Studies have suggested aberrant transcription factor function and epigenetic regulation can explain differences between B-ALL subtypes; however, the impact of 3D genome reorganization remains unclear. In this study, we used in situ Hi-C and RNA sequencing to profile the chromatin architectural landscape in healthy B-cell progenitors and B-ALL patient samples harboring prognostically relevant structural variations, including ETV6::RUNX1, KMT2A::AFF1, and BCR::ABL. We showed that B-ALLs undergo subtype-specific changes that, in part, reflect the differentiation stage of the disease and that they acquire aberrant chromatin configurations that allow the expression of oncogenic drivers. One such driver, ERG, displayed increased interactivity and expression in ETV6::RUNX1 B-ALL, and evidence suggests that it plays a role in regulating survival and differentiation. Overall, these results underscore the essential role of 3D nuclear organization in acute leukemia.Significance: Our integrative analyses of 3D chromatin architecture, accessibility, and gene expression in normal and malignant human B cells revealed an evolution of 3D genome architecture and associated transcription programs that may drive the differentiation of normal B cells as well as the transformation of B-ALL subtypes. See related commentary by Gruber, p. 509.","PeriodicalId":29944,"journal":{"name":"Blood Cancer Discovery","volume":" ","pages":"586-605"},"PeriodicalIF":12.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147692582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0