Ji Xinyao, Yang Cheng, Niu Changchun
Department of Laboratory Medicine, Chongqing General Hospital, Chongqing University, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China.
Department of Laboratory Medicine, Chongqing General Hospital, No.118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, China.
BMC Cancer. 2024 Dec 18;24(1):1545. doi: 10.1186/s12885-024-13286-3.
Aim to investigate the multi-omic characteristics of the bone marrow supernatant of relapsed acute myeloid leukemia (AML) and search for proteins and metabolites associated with relapse.
A total of 40 bone marrow supernatant from 7 patients with relapsed AML and 33 patients with non-relapsed AML were collected for proteomics and metabonomics analysis. Unsupervised clustering was used to discover the characteristics of proteins and metabolites. The prognostic significances of proteins were assessed concerning the relapse status(including death) and relapse-free survival.
Totally 996 proteins and 4,831 metabolites were identified in bone marrow supernatant, and two of 7 clusters were revealed through unsupervised clustering and were associated with ASXL1, TP53, and RUNX1 mutations, which were listed as high-risk factors in the 2022 edition of the WHO classification of tumors of the hematopoietic and lymphoid tissues. Among the identified proteins and metabolites, 57 proteins and 190 metabolites were found to be closely related to relapse.
This study has revealed a significant correlation between protein expression in the bone marrow microenvironment of AML and three high-risk mutations: ASXL1, TP53, and RUNX1. Based on this finding, we further identified 227 differential proteins closely associated with these three mutations, as well as 57 proteins directly related to disease recurrence. Additionally, lipid metabolism plays a crucial role in the occurrence and development of AML within its bone marrow microenvironment.
旨在研究复发性急性髓系白血病（AML）骨髓上清液的多组学特征，并寻找与复发相关的蛋白质和代谢物。
收集7例复发性AML患者和33例非复发性AML患者的共40份骨髓上清液进行蛋白质组学和代谢组学分析。采用无监督聚类来发现蛋白质和代谢物的特征。评估蛋白质对复发状态（包括死亡）和无复发生存的预后意义。
在骨髓上清液中总共鉴定出996种蛋白质和4831种代谢物，通过无监督聚类揭示了7个聚类中的2个，并与ASXL1、TP53和RUNX1突变相关，这些突变在2022年版世界卫生组织造血与淋巴组织肿瘤分类中被列为高危因素。在鉴定出的蛋白质和代谢物中，发现57种蛋白质和190种代谢物与复发密切相关。
本研究揭示了AML骨髓微环境中的蛋白质表达与三种高危突变ASXL1、TP53和RUNX1之间存在显著相关性。基于这一发现，我们进一步鉴定出与这三种突变密切相关的227种差异蛋白质，以及与疾病复发直接相关的57种蛋白质。此外，脂质代谢在AML骨髓微环境中的发生和发展中起着关键作用。
