Haematologica最新文献_第8页

Lysine succinylation precisely controls normal erythropoiesis. 赖氨酸琥珀酰化可精确控制正常的红细胞生成。

IF 10.1 1区医学

Haematologica Pub Date : 2024-10-17 DOI: 10.3324/haematol.2024.285752

Bin Hu,Han Gong,Ling Nie,Ji Zhang,Yanan Li,Dandan Liu,Huifang Zhang,Haihang Zhang,Lu Han,Chaoying Yang,Maohua Li,Wenwen Xu,Yukio Nakamura,Lihong Shi,Mao Ye,Christopher D Hillyer,Narla Mohandas,Long Liang,Yue Sheng,Jing Liu

{"title":"Lysine succinylation precisely controls normal erythropoiesis.","authors":"Bin Hu,Han Gong,Ling Nie,Ji Zhang,Yanan Li,Dandan Liu,Huifang Zhang,Haihang Zhang,Lu Han,Chaoying Yang,Maohua Li,Wenwen Xu,Yukio Nakamura,Lihong Shi,Mao Ye,Christopher D Hillyer,Narla Mohandas,Long Liang,Yue Sheng,Jing Liu","doi":"10.3324/haematol.2024.285752","DOIUrl":"https://doi.org/10.3324/haematol.2024.285752","url":null,"abstract":"Lysine succinylation (Ksu) has recently emerged as a protein modification that regulates diverse functions in various biological processes. However, the systemically and precise role of lysine succinylation in erythropoiesis remains to be fully elucidated. In this study, we noted a prominent increase of succinyl-CoA and lysine succinylation during human erythroid differentiation. To explore the functional significance of succinylation, we inhibited succinylation by either knock downing key succinyltransferases or overexpressing desuccinylases. Succinylation inhibition led to suppressed cell proliferation, increased apoptosis, and disrupted erythroid differentiation. In vivo overexpression of the desuccinylases SIRT5 delayed erythroid differentiation. Furthermore, integrative proteome and succinylome analysis identifies 939 succinylated proteins with 3,562 Ksu sites, distributed across various cellular compartments and involved in multiple cellular processes. Significantly, inconsistencies between protein expression levels and succinylation levels were observed, indicating that the succinylation of certain proteins may function independently of expression. Mechanistically, we implicated KAT2A-mediated succinylation of histone H3 K79, leading to chromatin remodeling and subsequently erythropoiesis regulation. Specially, we identified CYCS as a key regulator of erythropoiesis, which depends on its succinylation sites K28/K40. Taken together, our comprehensive investigation of the succinylation landscape during erythropoiesis provides valuable insights into its regulatory role and offer potential implications for erythroid-related diseases.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":10.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448039","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

Severe acute cutaneous only graft-versus-host disease after late relapse of chronic myeloid leukemia and ultraviolet B phototherapy. 慢性髓性白血病晚期复发并接受紫外线 B 光疗后出现的严重急性皮肤移植物抗宿主病。

IF 10.1 1区医学

Haematologica Pub Date : 2024-10-17 DOI: 10.3324/haematol.2024.286369

J Scott Beeler,Rahul Peravali,Kristan M Augustin,Amy C M Musiek,Kiran Vij,Dilan A Patel,John F DiPersio

引用次数: 0

Different inflammatory, fibrotic, and immunologic signatures between pre-fibrotic and overt primary myelofibrosis. 纤维化前期和原发性骨髓纤维化之间存在不同的炎症、纤维化和免疫学特征。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.285598

Seung-Hyun Jung, Sung-Eun Lee, Sujin Yun, Da-Eun Min, Youngjin Shin, Yeun-Jun Chung, Sug Hyung Lee

{"title":"Different inflammatory, fibrotic, and immunologic signatures between pre-fibrotic and overt primary myelofibrosis.","authors":"Seung-Hyun Jung, Sung-Eun Lee, Sujin Yun, Da-Eun Min, Youngjin Shin, Yeun-Jun Chung, Sug Hyung Lee","doi":"10.3324/haematol.2024.285598","DOIUrl":"https://doi.org/10.3324/haematol.2024.285598","url":null,"abstract":"Primary myelofibrosis (PMF) is a myeloid proliferative neoplasm (MPN) characterized by bone marrow (BM) fibrosis. Pre-fibrotic PMF (pre-PMF) progresses to overt PMF. Megakaryocytes (MKs) play a primary role in PMF; however, the functions of MK subsets and those of other hematopoietic cells during PMF progression remain unclarified. Therefore, we analyzed BM aspirates in pre-PMFs, overt PMFs, and other MPNs using single-cell RNA sequencing (scRNA-seq). We identified 14 cell types with subsets, including hematopoietic stem and progenitor cells (HSPCs) and MKs. HSPCs in overt PMF were MK-biased and inflammation/fibrosis-enriched. Among MKs, the epithelial-mesenchymal transition (EMT)-enriched subset was abruptly increased in overt PMF. MKs in non-fibrotic/non-PMF MPN were MK differentiation-enriched, whereas those in fibrotic/non-PMF MPN were inflammation/fibrosis-enriched. Overall, the inflammation/fibrosis signatures of the HSPC, MK, and CD14+ monocyte subsets increased from pre-PMF to overt PMF. Cytotoxic and dysfunctional scores also increased in T and NK cells. Clinically, MK and HSPC subsets with high inflammation/fibrosis signatures were frequent in the patients with peripheral blood blasts ≥1%. scRNA-seq predicted higher cellular communications of MK differentiation, inflammation/fibrosis, immunologic effector/dysfunction, and tumor-associated signaling in overt PMF than pre-PMF. However, no decisive subset emerged during PMF progression. Our study demonstrated that HSPCs, monocytes, and lymphoid cells contribute to PMF progression, and subset specificity existed regarding inflammation/fibrosis and immunologic dysfunction. PMF progression may depend on multiple cell types' alterations, and EMTenriched MKs may be potential targets for the diagnosis and therapy of the progression.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390070","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

CODOX-M/IVAC-R versus DA-EPOCH-R in double hit/triple hit lymphoma patients aged 60 years or under. CODOX-M/IVAC-R与DA-EPOCH-R在60岁或以下的双击/三击淋巴瘤患者中的对比。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.286168

Suheil Albert Atallah-Yunes, Matthew J Rees, Thomas E Witzig, Thomas M Habermann, Javier Munoz, Madiha Iqbal, Ellen D McPhail, Grzegorz S Nowakowski

{"title":"CODOX-M/IVAC-R versus DA-EPOCH-R in double hit/triple hit lymphoma patients aged 60 years or under.","authors":"Suheil Albert Atallah-Yunes, Matthew J Rees, Thomas E Witzig, Thomas M Habermann, Javier Munoz, Madiha Iqbal, Ellen D McPhail, Grzegorz S Nowakowski","doi":"10.3324/haematol.2024.286168","DOIUrl":"https://doi.org/10.3324/haematol.2024.286168","url":null,"abstract":"Intensified chemoimmunotherapy regimens are often used in young patients with double hit and triple hit lymphoma (DHL/THL) despite no survival benefit compared to R-CHOP. Favorable retrospective reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate this treatment. We conducted a retrospective analysis to investigate outcome differences between CODOX-M/IVAC-R and DA-EPOCH-R in DHL/THL patients aged 60 years or younger. 113 patients were identified; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). 80% (39/49) achieved complete (CR) after completing CODOX-M/IVAC-R compared to 58% (37/64) with DA-EPOCH-R. The median follow-up was 5.3 years and 3.3 years for the CODOX-M/IVAC-R and DA-EPOCH-R group respectively. CODOX-M/IVAC-R demonstrated superior EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL translocation (BCL2 vs BCL6 vs both), IPI score and receipt of ASCT (aHR=0.52, 95%CI=0.29-0.93); however there was no significant influence on OS (aHR=0.92, 95%CI=0.46-1.84). The 1, 2 and 5 years EFS in the CODOX-M/IVAC-R group was 68.3%, 64.1% and 61.5% respectively compared to 52.4%, 48.9% and 39.5% respectively in the DA-EPOCH-R group. Primary refractory disease or relapse occurred in 33% (16/49) of CODOX-M/IVAC-R and 54% (35/64) of DA-EPOCH-R recipients, and produced median OS of 10.3 months and 33.7 months, respectively, indicating poor outcomes in the CODOX-M/IVAC-R subgroup with R/R disease. More patients were able to receive subsequent salvage therapies in the DA-EPOCH-R group. No patients died of regimen toxicity and the rates of CNS relapse and therapy related hematologic neoplasms were similar in both groups.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390068","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

Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses. 细胞周期蛋白 C 通过抵消 p53 介导的应激反应，促进 B 细胞急性淋巴细胞白血病的发展和恶化。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.285701

Jana Trifinopoulos, Julia List, Thorsten Klampfl, Klara Klein, Michaela Prchal-Murphy, Agnieszka Witalisz-Siepracka, Florian Bellutti, Luca L Fava, Gerwin Heller, Sarah Stummer, Patricia Testori, Monique L Den Boer, Judith M Boer, Sonja Marinovic, Gregor Hoermann, Wencke Walter, Andreas Villunger, Piotr Sicinski, Veronika Sexl, Dagmar Gotthardt

{"title":"Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses.","authors":"Jana Trifinopoulos, Julia List, Thorsten Klampfl, Klara Klein, Michaela Prchal-Murphy, Agnieszka Witalisz-Siepracka, Florian Bellutti, Luca L Fava, Gerwin Heller, Sarah Stummer, Patricia Testori, Monique L Den Boer, Judith M Boer, Sonja Marinovic, Gregor Hoermann, Wencke Walter, Andreas Villunger, Piotr Sicinski, Veronika Sexl, Dagmar Gotthardt","doi":"10.3324/haematol.2024.285701","DOIUrl":"https://doi.org/10.3324/haematol.2024.285701","url":null,"abstract":"Despite major therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL), resistances and long-term toxicities still pose significant challenges. Cyclins and their associated cyclin-dependent kinases are one focus of cancer research when looking for targeted therapies. We discovered cyclin C as a key factor for B-ALL development and maintenance. While cyclin C is non-essential for normal hematopoiesis, CcncΔ/Δ BCR::ABL1+ B-ALL cells fail to elicit leukemia in mice. RNA sequencing experiments revealed a p53 pathway deregulation in CcncΔ/Δ BCR::ABL1+ cells resulting in the incapability of the leukemic cells to adequately respond to stress. A genome-wide CRISPR/Cas9 loss-of-function screen supplemented with additional knock-outs unveiled a dependency of human B-lymphoid cell lines on CCNC. High cyclin C levels in B-cell precursor (BCP) ALL patients were associated with poor event-free survival and increased risk of early disease recurrence after remission. Our findings highlight cyclin C as potential therapeutic target for B-ALL, particularly to enhance cancer cell sensitivity to stress and chemotherapy.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390069","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

Long-term survival can be achieved in a significant fraction of older patients with core binding factor acute myeloid leukemia treated with intensive chemotherapy. 在接受强化化疗的核心结合因子急性髓性白血病老年患者中，有相当一部分可以获得长期生存。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.285448

Federico Mosna, Erika Borlenghi, Mark Litzow, John C Byrd, Cristina Papayannidis, Cristina Tecchio, Felicetto Ferrara, Guido Marcucci, Roberto Cairoli, Elizabeth A Morgan, Carmela Gurrieri, Cecilia C S Yeung, H Joachim Deeg, Debora Capelli, Anna Candoni, Jason R Gotlib, Monia Lunghi, Sheeja Pullarkat, Francesco Lanza, Sara Galimberti, Fabio Forghieri, Adriano Venditti, Moreno Festuccia, Ernesta Audisio, Denise Marvalle, Gian Matteo Rigolin, Giovanni Roti, Eros DiBona, Giuseppe Visani, Francesco Albano, Ann-Kathrin Eisfeld, Peter Valent, Gerwin Huls, Gautam Borthakur, Mauro Krampera, Giovanni Martinelli, Nicolaus Kröger, Alessandra Sperotto, Michele Gottardi

{"title":"Long-term survival can be achieved in a significant fraction of older patients with core binding factor acute myeloid leukemia treated with intensive chemotherapy.","authors":"Federico Mosna, Erika Borlenghi, Mark Litzow, John C Byrd, Cristina Papayannidis, Cristina Tecchio, Felicetto Ferrara, Guido Marcucci, Roberto Cairoli, Elizabeth A Morgan, Carmela Gurrieri, Cecilia C S Yeung, H Joachim Deeg, Debora Capelli, Anna Candoni, Jason R Gotlib, Monia Lunghi, Sheeja Pullarkat, Francesco Lanza, Sara Galimberti, Fabio Forghieri, Adriano Venditti, Moreno Festuccia, Ernesta Audisio, Denise Marvalle, Gian Matteo Rigolin, Giovanni Roti, Eros DiBona, Giuseppe Visani, Francesco Albano, Ann-Kathrin Eisfeld, Peter Valent, Gerwin Huls, Gautam Borthakur, Mauro Krampera, Giovanni Martinelli, Nicolaus Kröger, Alessandra Sperotto, Michele Gottardi","doi":"10.3324/haematol.2024.285448","DOIUrl":"https://doi.org/10.3324/haematol.2024.285448","url":null,"abstract":"Acute Myeloid Leukemia is mainly a disease of the elderly: however, the knowledge on the outcomes of treatment in core binding factor AML (CBFAML) in older population, is limited. We retrospectively collected data on 229 patients with CBF- AML followed long-term in the last two decades. A 5-year overall survival (OS) of 44.2% (95%CI, 39.9-47.5) and a 5-year event - free survival (EFS) of 32.9% (95%CI, 25.5-40.1) was observed. In a subgroup of >70-year patients who completed intensive therapy (induction + >3 courses of consolidation including autologous stem cell transplant: 10 patients) the median EFS was 11.8 months (95%CI, 9.4 - 15.2) and OS was 40.0% (95%CI, 36.4 - 44.1) at 5yr. In univariate analysis, age >70 (hazard ratio (HR) 1.78, [95%CI, 1.15 - 2.54], p=.008), failure to achieve remission following induction (HR, 8.96 [95%CI, 5.5 - 13.8], p=<.0001), no consolidation therapy (HR, 0.75 [95%CI, 0.47 - 1.84], p=.04) and less than 3 cycles of consolidation (HR, 1.48 [95%CI, 0.75 - 3.2], p=.0004), predicted poorer EFS. Our study shows that intensive therapy, in selected older CBF-AML patients, leads to longer survival. Achieving a CR seems to be the most important first step and at least 3 cycles of consolidation, an important second one. The analysis suggests that these patients should not be excluded from studies with intensive therapies.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390073","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

Artificial intelligence-based Myelodysplastic Syndromes Score, 2022 classifications, and the Molecular International Prognostic Scoring System : a perfect match. 基于人工智能的骨髓增生异常综合征评分、2022 分类和国际分子预后评分系统：完美匹配。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.286340

Valentin Clichet, Thomas Boyer

引用次数: 0

Expression levels of genes implicated in the working mechanism of lenalidomide predict treatment response in lower risk myelodysplastic syndrome patients. 来那度胺作用机制相关基因的表达水平可预测低风险骨髓增生异常综合征患者的治疗反应。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.286157

Florentien E M In 't Hout, Thessa N Scheele, Theresia M Westers, Canan Alhan, Carolien Duetz, Eline M P Cremers, Heleen A Visser-Wisselaar, Annelies Verbrugge, Dana A Chitu, Bert A Van der Reijden, Aniek O De Graaf, Arjan A Van de Loosdrecht, Joop H Jansen

引用次数: 0

HDAC6 inhibitors sensitize resistant t(11;14) multiple myeloma cells to a combination of bortezomib and BH3 mimetics. HDAC6抑制剂能使耐药的t(11;14)多发性骨髓瘤细胞对硼替佐米和BH3模拟物联合疗法敏感。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.286279

Cristina Florean, Manon Lernoux, Anne Lorant, Helene Losson, Guy Bormans, Michael Schnekenburger, Marc Diederich

引用次数: 0

Challenges in defining the immune microenvironment in T-cell lymphoma. 确定 T 细胞淋巴瘤免疫微环境的挑战。

IF 8.2 1区医学

Haematologica Pub Date : 2024-10-10 DOI: 10.3324/haematol.2024.285836

Ahmet Dogan, Mikhail Roshal

引用次数: 0