Proteomic profiling of plasma exosomes from patients with B-cell acute lymphoblastic leukemia

Shicong Zhu; Cheng Xing; Ruijuan Li; Zhao Cheng; Mingyang Deng; Yunya Luo; Heng Li; Guangsen Zhang; Yue Sheng; Hongling Peng; Zhihua Wang

doi:10.1038/s41598-022-16282-4

Proteomic profiling of plasma exosomes from patients with B-cell acute lymphoblastic leukemia

Sci Rep. 2022 Jul 13;12(1):11975. doi: 10.1038/s41598-022-16282-4.

Authors

Shicong Zhu¹, Cheng Xing^{2

3}, Ruijuan Li^{2

3}, Zhao Cheng^{2

3}, Mingyang Deng^{2

3}, Yunya Luo^{2

3}, Heng Li^{2

3}, Guangsen Zhang^{2

3}, Yue Sheng^{2

3}, Hongling Peng^{2

3}, Zhihua Wang^{4

5}

Affiliations

¹ Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Institute of Molecular Hematology, Central South University, Changsha, Hunan, China.
⁴ Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. wangzhihuazsc@csu.edu.cn.
⁵ Institute of Molecular Hematology, Central South University, Changsha, Hunan, China. wangzhihuazsc@csu.edu.cn.

Abstract

We aimed to comprehensively investigate the proteomic profile and underlying biological function of exosomal proteins associated with B-cell acute lymphoblastic leukemia. Exosomes were isolated from plasma samples collected from five patients with B-ALL and five healthy individuals, and their protein content was quantitatively analyzed by liquid chromatography with tandem mass spectrometry. A total of 342 differentially expressed proteins were identified in patients with B-ALL. The DEPs were mainly associated with protein metabolic processes and protein activity regulation and were significantly enriched in the Notch and autophagy pathways. Furthermore, we found that ADAM17 and ATG3 were upregulated in patients with B-ALL and enriched in the Notch and autophagy pathways, respectively. Further western blot analysis of exosomes collected from additional 18 patients with B-ALL and 10 healthy controls confirmed that both ADAM17 and ATG3 were overexpressed in exosomes derived from patients with B-ALL (p < 0.001). The areas under the curves of ADAM17 and ATG3 were 0.989 and 0.956, respectively, demonstrating their diagnostic potential. In conclusion, ADAM17 and ATG3 in plasma-derived exosomes may contribute to the progression of B-ALL by regulating the Notch and autophagy pathways. Hence, these proteins may represent valuable diagnostic biomarkers and therapeutic targets for B-ALL.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chromatography, Liquid
Exosomes* / metabolism
Humans
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / metabolism
Proteomics / methods
Tandem Mass Spectrometry