Proteomic Profiling of Plasma Exosomes from Patients with B-cell Acute Lymphoblastic Leukemia

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jul 13

PMID 35831551

Authors

Shicong Zhu

Cheng Xing

Ruijuan Li

Zhao Cheng

Mingyang Deng

Yunya Luo

Heng Li

Guangsen Zhang

Yue Sheng

Hongling Peng

Zhihua Wang

Affiliations

Soon will be listed here.

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.

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References

Baker F, Polat I, Abou-El-Ardat K, Alshamleh I, Thoelken M, Hymon D . Metabolic Rewiring Is Essential for AML Cell Survival to Overcome Autophagy Inhibition by Loss of ATG3. Cancers (Basel). 2021; 13(23). PMC: 8657081. DOI: 10.3390/cancers13236142. View

Pagliaro L, Marchesini M, Roti G . Targeting oncogenic Notch signaling with SERCA inhibitors. J Hematol Oncol. 2021; 14(1):8. PMC: 7789735. DOI: 10.1186/s13045-020-01015-9. View

Kalluri R, LeBleu V . The biology function and biomedical applications of exosomes. Science. 2020; 367(6478). PMC: 7717626. DOI: 10.1126/science.aau6977. View

Li T, Huang Y, Zhou W, Yan Q . Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells. Biomed Res Int. 2020; 2020:6069390. PMC: 7102475. DOI: 10.1155/2020/6069390. View

Hessvik N, Llorente A . Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2017; 75(2):193-208. PMC: 5756260. DOI: 10.1007/s00018-017-2595-9. View

Huang F, Yu S, Li C . Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia. Cancer Control. 2021; 28:10732748211019138. PMC: 8236760. DOI: 10.1177/10732748211019138. View

Kuriyama H, Fukushima S, Kimura T, Okada E, Ishibashi T, Mizuhashi S . Matrin-3 plays an important role in cell cycle and apoptosis for survival in malignant melanoma. J Dermatol Sci. 2020; 100(2):110-119. DOI: 10.1016/j.jdermsci.2020.08.013. View

Christian L . The ADAM family: Insights into Notch proteolysis. Fly (Austin). 2012; 6(1):30-4. DOI: 10.4161/fly.18823. View

Kanehisa M . Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019; 28(11):1947-1951. PMC: 6798127. DOI: 10.1002/pro.3715. View

10.

Nwabo Kamdje A, Mosna F, Bifari F, Lisi V, Bassi G, Malpeli G . Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells. Blood. 2011; 118(2):380-9. DOI: 10.1182/blood-2010-12-326694. View

11.

Bride K, Hu H, Tikhonova A, Fuller T, Vincent T, Shraim R . Rational drug combinations with CDK4/6 inhibitors in acute lymphoblastic leukemia. Haematologica. 2021; 107(8):1746-1757. PMC: 9335101. DOI: 10.3324/haematol.2021.279410. View

12.

Li W, Wang D, Sun X, Zhang Y, Wang L, Suo J . ADAM17 promotes lymph node metastasis in gastric cancer via activation of the Notch and Wnt signaling pathways. Int J Mol Med. 2018; 43(2):914-926. PMC: 6317666. DOI: 10.3892/ijmm.2018.4028. View

13.

Ntziachristos P, Lim J, Sage J, Aifantis I . From fly wings to targeted cancer therapies: a centennial for notch signaling. Cancer Cell. 2014; 25(3):318-34. PMC: 4040351. DOI: 10.1016/j.ccr.2014.02.018. View

14.

Caescu C, Jeschke G, Turk B . Active-site determinants of substrate recognition by the metalloproteinases TACE and ADAM10. Biochem J. 2009; 424(1):79-88. PMC: 2774824. DOI: 10.1042/BJ20090549. View

15.

Grotzinger J, Lorenzen I, Dusterhoft S . Molecular insights into the multilayered regulation of ADAM17: The role of the extracellular region. Biochim Biophys Acta Mol Cell Res. 2017; 1864(11 Pt B):2088-2095. DOI: 10.1016/j.bbamcr.2017.05.024. View

16.

Sun L, Wan A, Zhou Z, Chen D, Liang H, Liu C . RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer. Gut. 2020; 70(9):1698-1712. PMC: 8355885. DOI: 10.1136/gutjnl-2020-320652. View

17.

Bellavia D, Palermo R, Felli M, Screpanti I, Checquolo S . Notch signaling as a therapeutic target for acute lymphoblastic leukemia. Expert Opin Ther Targets. 2018; 22(4):331-342. DOI: 10.1080/14728222.2018.1451840. View

18.

Li D, Li T, Shang Z, Zhao L, Xu Q, Tan J . Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITD acute myeloid leukemia. Signal Transduct Target Ther. 2020; 5(1):21. PMC: 7067872. DOI: 10.1038/s41392-020-0108-z. View

19.

Sebestyen E, Singh B, Minana B, Pages A, Mateo F, Pujana M . Corrigendum: Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks. Genome Res. 2018; 28(9):1426. PMC: 6120636. DOI: 10.1101/gr.242214.118. View

20.

Li G, Lei X, Zhang Y, Liu Z, Zhu K . LncRNA PPM1A-AS Regulate Tumor Development Through Multiple Signal Pathways in T-Cell Acute Lymphoblastic Leukemia. Front Oncol. 2021; 11:761205. PMC: 8567141. DOI: 10.3389/fonc.2021.761205. View