OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine.

IF 2.5 3区 医学 Q3 ONCOLOGY World Journal of Surgical Oncology Pub Date : 2024-11-12 DOI:10.1186/s12957-024-03581-5
Amal Kamal Abdel-Aziz
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Abstract

Background: Despite significant advances in comprehending its tumorigenic role, the prognostic and therapeutic potential of targeting oxidative phosphorylation (OXPHOS) in acute myeloid leukemia (AML) remain obscure.

Methods: The prognostic value of ~ 200 mitochondrial/OXPHOS genes as candidate biomarkers was examined in AML patients over ~ 10 years follow-up using Kaplan-Meier and Cox regression analyses. Furthermore, the transcript levels of the assessed markers were inspected in healthy bone marrow tissues and the dependencies of AML cells on the assessed genes were examined.

Results: Elevated levels of NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6), succinate dehydrogenase complex flavoprotein subunit A (SDHA), solute carrier family 25 member 12 (SLC25A12), electron transfer flavoprotein subunit beta (ETFB), carnitine palmitoyltransferase 1A (CPT1A) and glutathione peroxidase 4 (GPX4) were associated with poor overall survival of AML patients. SLC25A12, ETFB and CPT1A were overexpressed in AML compared to healthy tissues. Cytochrome B5 type A (CYB5A)high, SLC25A12high and GPX4high AML patients displayed higher levels of circulating and engrafted blasts compared to low-expressing cohorts. NPM1 and SRSF2 mutations were frequent in SDHAlow and CPT1Alow AML patients respectively. FLT3-ITD, NPM1 and IDH1 mutations were prevalent in CPT1Ahigh AML patients. FLT3-ITD AMLs were more dependent on OXPHOS.

Conclusions: This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.

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急性髓性白血病患者体内的 OXPHOS 介质:个性化医疗的预后生物标志物和治疗靶点。
背景:尽管在理解氧化磷酸化(OXPHOS)的致瘤作用方面取得了重大进展,但针对急性髓性白血病(AML)的氧化磷酸化(OXPHOS)的预后和治疗潜力仍不明显:方法:使用 Kaplan-Meier 和 Cox 回归分析法研究了约 200 个线粒体/OXPHOS 基因作为候选生物标志物对随访约 10 年的急性髓性白血病患者的预后价值。此外,还检测了健康骨髓组织中评估标志物的转录水平,并研究了 AML 细胞对评估基因的依赖性:结果:NADH:泛醌氧化还原酶亚基A6(NDUFA6)、琥珀酸脱氢酶复合物黄蛋白亚基A(SDHA)、溶质运载家族25成员12(SLC25A12)、电子传递黄蛋白亚基β(ETFB)、肉碱棕榈酰基转移酶1A(CPT1A)和谷胱甘肽过氧化物酶4(GPX4)的水平升高与急性髓细胞白血病患者的总生存率较低有关。与健康组织相比,SLC25A12、ETFB 和 CPT1A 在急性髓细胞性白血病中过表达。与低表达组相比,细胞色素B5 A型(CYB5A)高、SLC25A12高和GPX4高的急性髓细胞性白血病患者的循环和移植囊泡水平更高。NPM1和SRSF2突变分别在SDHA低和CPT1A低的急性髓细胞性白血病患者中很常见。FLT3-ITD、NPM1和IDH1突变在CPT1A高的急性髓细胞性白血病患者中很常见。FLT3-ITD型急性髓细胞性白血病更依赖于OXPHOS:本研究发现NDUFA6和SDHA是新型的辅助预后生物标志物,可为急性髓细胞性白血病患者的个性化治疗提供合理的策略。
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来源期刊
CiteScore
4.70
自引率
15.60%
发文量
362
审稿时长
3 months
期刊介绍: World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.
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