线粒体碎片是骨髓增生异常综合征的新治疗靶点和诊断标准。

IF 0.7 Q4 HEMATOLOGY Leukemia Research Reports Pub Date : 2024-01-01 DOI:10.1016/j.lrr.2024.100424
Y. Kamimura-Aoyagi , Y. Harada , K. Nomura , N. Matsunuma , K. Yuki , H. Kobayashi , Y. Hayashi , A. Hijikata , H. Harada
{"title":"线粒体碎片是骨髓增生异常综合征的新治疗靶点和诊断标准。","authors":"Y. Kamimura-Aoyagi ,&nbsp;Y. Harada ,&nbsp;K. Nomura ,&nbsp;N. Matsunuma ,&nbsp;K. Yuki ,&nbsp;H. Kobayashi ,&nbsp;Y. Hayashi ,&nbsp;A. Hijikata ,&nbsp;H. Harada","doi":"10.1016/j.lrr.2024.100424","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Myelodysplastic syndromes (MDS) are characterized by persistent of cytopenia, gene abnormalities, and dysplasia. Although the correlation between chronic inflammation and ineffective hematopoiesis is demonstrated in forming MDS pathogenesis, the detailed mechanisms remain unclear.</p></div><div><h3>Methods</h3><p>Recently, we established a new MDS with low blasts (MDS-LB) model (<em>CBL<sup>ΔE8/9</sup>-RUNX1<sup>S291fs</sup></em> mice) , which recapitulates MDS-LB pathogenesis such as pancytopenia and chronic inflammation, by introducing these two mutations into murine hematopoietic stem and progenitor cells (HSC/Ps) .</p></div><div><h3>Results</h3><p>MDS model mice exhibited excessive mitochondrial fragmentation due to Drp1 activation in HSC/Ps. Importantly, pharmacological inhibition of mitochondrial fragmentation rescued leukocytopenia and dysplasia formation in MDS mice by suppressing inflammatory signaling activation, suggesting that mitochondrial fragmentation could be a new therapeutic target of MDS. Given that mitochondrial fragmentation is related to MDS pathogenesis, we hypothesized that mitochondrial fragmentation can be used for morphological diagnosis of MDS. Differential diagnosis of patients with non-MDS cytopenia and MDS-LB has been challenging. We assessed mitochondrial morphology in bone marrow samples from 10 healthy individuals and 141 patients before disease-modifying therapy. The percentage of cells with mitochondrial fragmentation was significantly increased in patients with MDS-LB, compared with that in patients with cytopenia without dysplasia and gene abnormality (mean 50.7% vs 22.4%, P&lt;0.001, cutoff value 30.8%). The calculated cutoff value clearly distinguishes patients with MDS-LB and non-MDS cytopenia.</p></div><div><h3>Conclusions</h3><p>These data suggest that mitochondrial fragmentation can be not only a new therapeutic target of MDS-LB but also one category of dysplasia that can diagnose MDS-LB.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000141/pdfft?md5=eaf437a90e97a820f57941330d565a3f&pid=1-s2.0-S2213048924000141-main.pdf","citationCount":"0","resultStr":"{\"title\":\"MITOCHONDRIAL FRAGMENTATION IS A NEW THERAPEUTIC TARGET AND DIAGNOSTIC CRITERIA FOR MYELODYSPLASTIC SYNDROMES.\",\"authors\":\"Y. Kamimura-Aoyagi ,&nbsp;Y. Harada ,&nbsp;K. Nomura ,&nbsp;N. Matsunuma ,&nbsp;K. Yuki ,&nbsp;H. Kobayashi ,&nbsp;Y. Hayashi ,&nbsp;A. Hijikata ,&nbsp;H. Harada\",\"doi\":\"10.1016/j.lrr.2024.100424\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Myelodysplastic syndromes (MDS) are characterized by persistent of cytopenia, gene abnormalities, and dysplasia. Although the correlation between chronic inflammation and ineffective hematopoiesis is demonstrated in forming MDS pathogenesis, the detailed mechanisms remain unclear.</p></div><div><h3>Methods</h3><p>Recently, we established a new MDS with low blasts (MDS-LB) model (<em>CBL<sup>ΔE8/9</sup>-RUNX1<sup>S291fs</sup></em> mice) , which recapitulates MDS-LB pathogenesis such as pancytopenia and chronic inflammation, by introducing these two mutations into murine hematopoietic stem and progenitor cells (HSC/Ps) .</p></div><div><h3>Results</h3><p>MDS model mice exhibited excessive mitochondrial fragmentation due to Drp1 activation in HSC/Ps. Importantly, pharmacological inhibition of mitochondrial fragmentation rescued leukocytopenia and dysplasia formation in MDS mice by suppressing inflammatory signaling activation, suggesting that mitochondrial fragmentation could be a new therapeutic target of MDS. Given that mitochondrial fragmentation is related to MDS pathogenesis, we hypothesized that mitochondrial fragmentation can be used for morphological diagnosis of MDS. Differential diagnosis of patients with non-MDS cytopenia and MDS-LB has been challenging. We assessed mitochondrial morphology in bone marrow samples from 10 healthy individuals and 141 patients before disease-modifying therapy. The percentage of cells with mitochondrial fragmentation was significantly increased in patients with MDS-LB, compared with that in patients with cytopenia without dysplasia and gene abnormality (mean 50.7% vs 22.4%, P&lt;0.001, cutoff value 30.8%). The calculated cutoff value clearly distinguishes patients with MDS-LB and non-MDS cytopenia.</p></div><div><h3>Conclusions</h3><p>These data suggest that mitochondrial fragmentation can be not only a new therapeutic target of MDS-LB but also one category of dysplasia that can diagnose MDS-LB.</p></div>\",\"PeriodicalId\":38435,\"journal\":{\"name\":\"Leukemia Research Reports\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.7000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2213048924000141/pdfft?md5=eaf437a90e97a820f57941330d565a3f&pid=1-s2.0-S2213048924000141-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia Research Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213048924000141\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213048924000141","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

导言 骨髓增生异常综合征(MDS)的特征是持续的全血细胞减少、基因异常和发育不良。虽然慢性炎症和无效造血之间的相关性已被证实是 MDS 的发病机制,但其具体机制仍不清楚。方法最近,我们通过在小鼠造血干细胞和祖细胞(HSC/Ps)中引入这两个突变,建立了一种新的 MDS 低胚泡(MDS-LB)模型(CBLΔE8/9-RUNX1S291fs 小鼠),该模型再现了 MDS-LB 的发病机制,如泛血细胞减少和慢性炎症。重要的是,抑制线粒体碎片的药理作用通过抑制炎症信号激活来挽救 MDS 小鼠的白细胞减少症和发育不良的形成,这表明线粒体碎片可能是 MDS 的一个新的治疗靶点。鉴于线粒体碎片与 MDS 发病机制有关,我们假设线粒体碎片可用于 MDS 的形态学诊断。非 MDS 全血细胞减少症和 MDS-LB 患者的鉴别诊断一直具有挑战性。我们评估了 10 名健康人和 141 名接受疾病改变疗法前患者骨髓样本中的线粒体形态。与无发育不良和基因异常的全血细胞减少症患者相比,MDS-LB 患者线粒体破碎的细胞比例明显增加(平均 50.7% 对 22.4%,P<0.001,临界值 30.8%)。这些数据表明,线粒体碎片不仅是 MDS-LB 的一个新的治疗靶点,也是可以诊断 MDS-LB 的一类发育不良。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
MITOCHONDRIAL FRAGMENTATION IS A NEW THERAPEUTIC TARGET AND DIAGNOSTIC CRITERIA FOR MYELODYSPLASTIC SYNDROMES.

Introduction

Myelodysplastic syndromes (MDS) are characterized by persistent of cytopenia, gene abnormalities, and dysplasia. Although the correlation between chronic inflammation and ineffective hematopoiesis is demonstrated in forming MDS pathogenesis, the detailed mechanisms remain unclear.

Methods

Recently, we established a new MDS with low blasts (MDS-LB) model (CBLΔE8/9-RUNX1S291fs mice) , which recapitulates MDS-LB pathogenesis such as pancytopenia and chronic inflammation, by introducing these two mutations into murine hematopoietic stem and progenitor cells (HSC/Ps) .

Results

MDS model mice exhibited excessive mitochondrial fragmentation due to Drp1 activation in HSC/Ps. Importantly, pharmacological inhibition of mitochondrial fragmentation rescued leukocytopenia and dysplasia formation in MDS mice by suppressing inflammatory signaling activation, suggesting that mitochondrial fragmentation could be a new therapeutic target of MDS. Given that mitochondrial fragmentation is related to MDS pathogenesis, we hypothesized that mitochondrial fragmentation can be used for morphological diagnosis of MDS. Differential diagnosis of patients with non-MDS cytopenia and MDS-LB has been challenging. We assessed mitochondrial morphology in bone marrow samples from 10 healthy individuals and 141 patients before disease-modifying therapy. The percentage of cells with mitochondrial fragmentation was significantly increased in patients with MDS-LB, compared with that in patients with cytopenia without dysplasia and gene abnormality (mean 50.7% vs 22.4%, P<0.001, cutoff value 30.8%). The calculated cutoff value clearly distinguishes patients with MDS-LB and non-MDS cytopenia.

Conclusions

These data suggest that mitochondrial fragmentation can be not only a new therapeutic target of MDS-LB but also one category of dysplasia that can diagnose MDS-LB.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Leukemia Research Reports
Leukemia Research Reports Medicine-Oncology
CiteScore
1.70
自引率
0.00%
发文量
70
审稿时长
23 weeks
期刊最新文献
Late-onset Familial Hemophagocytic Lymphohistiocytosis in a survivor of Hodgkin's Lymphoma Posterior reversible encephalopathy syndrome (PRES) and myeloma IDH2-mutated near ETP-ALL with aggressive leukemia cutis and brisk response to venetoclax and decitabine Genomic heterogeneity within B/T mixed phenotype acute leukemia in a context of an immunophenotype Avapritinib treatment of aggressive systemic mastocytosis with a novel KIT exon 17 mutation
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1