Irradiation alters extracellular vesicle microRNA load in the serum of patients with leukaemia.
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Biomarker
Extracellular vesicles
Irradiation exposure
MiRNA
Journal
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]
ISSN: 1439-099X
Titre abrégé: Strahlenther Onkol
Pays: Germany
ID NLM: 8603469
Informations de publication
Date de publication:
26 Sep 2024
26 Sep 2024
Historique:
received:
04
07
2024
accepted:
09
09
2024
medline:
26
9
2024
pubmed:
26
9
2024
entrez:
26
9
2024
Statut:
aheadofprint
Résumé
Recent data suggest an impact of extracellular vesicles (EVs) and their micro(mi)RNA cargo on cell-cell interactions to contribute to pathophysiology of leukaemia and radiation response. Here, we investigated differential miRNA cargo of EVs from serum derived from patients with leukaemia (n = 11) before and after total body irradiation with 2 × 2 Gy as compared to healthy donors (n = 6). RNA was isolated from EVs and subjected to next generation sequencing of miRNAs. Analysis of sequencing data was performed with miRDeep29 software and differentially expressed miRNAs were filtered using R package edgeR10,11. Signaling pathways were identified using Kyoto Encyclopedia of Genes and Genomes database (KEGG) pathway analysis. Flow cytometric and Western blot analyses confirmed the presence of characteristic EV markers TSG-101, CD‑9 and CD-81. miRNA sequencing revealed a differential cargo in serum of patients with leukaemia in comparison to healthy donors with 23 significantly upregulated and 16 downregulated miRNAs affecting hedgehog, estrogen, glutathione metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathways amongst others. Whole body irradiation of patients with leukaemia significantly increased 11 miRNAs, involved in cell cycle regulation and platinum drug resistance, and decreased 15 miRNAs, contributing to apoptosis or cytokine-receptor interactions. As compared to healthy controls and following irradiation, we have identified differentially regulated miRNAs in serum-derived EVs from patients with leukaemia that may serve as possible biomarkers of leukaemic disease and treatment and radiation exposure.
Identifiants
pubmed: 39325141
doi: 10.1007/s00066-024-02307-6
pii: 10.1007/s00066-024-02307-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Bundesministerium für Bildung und Forschung
ID : 02NUK050D
Organisme : European Community
ID : 662287
Informations de copyright
© 2024. The Author(s).
Références
Choi JK, Xiao W, Chen X et al (2024) Fifth Edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues: Acute Lymphoblastic Leukemias, Mixed-Phenotype Acute Leukemias, Myeloid/Lymphoid Neoplasms With Eosinophilia, Dendritic/Histiocytic Neoplasms, and Genetic Tumor Syndromes. Mod Pathol 37:100466
doi: 10.1016/j.modpat.2024.100466
pubmed: 38460674
Malard F, Mohty M (2020) Acute lymphoblastic leukaemia. Lancet 395:1146–1162
doi: 10.1016/S0140-6736(19)33018-1
pubmed: 32247396
Dohner H, Wei AH, Appelbaum FR et al (2022) Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140:1345–1377
doi: 10.1182/blood.2022016867
pubmed: 35797463
Koschade SE, Stratmann JA, Finkelmeier F et al (2022) Relapse surveillance of acute myeloid leukemia patients in first remission after consolidation chemotherapy: diagnostic value of regular bone marrow aspirations. Ann Hematol 101:1703–1710
doi: 10.1007/s00277-022-04862-3
pubmed: 35595925
pmcid: 9279263
Abels ER, Breakefield XO (2016) Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol 36:301–312
doi: 10.1007/s10571-016-0366-z
pubmed: 27053351
pmcid: 5546313
Maas SLN, Breakefield XO, Weaver AM (2017) Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol 27:172–188
doi: 10.1016/j.tcb.2016.11.003
pubmed: 27979573
Kumar B, Garcia M, Murakami JL et al (2016) Exosome-mediated microenvironment dysregulation in leukemia. Biochim Biophys Acta 1863:464–470
doi: 10.1016/j.bbamcr.2015.09.017
pubmed: 26384870
Chen L, Xie T, Wei B et al (2023) Tumour-derived exosomes and their emerging roles in leukaemia (Review). Exp Ther Med 25:126
doi: 10.3892/etm.2023.11825
pubmed: 36845960
pmcid: 9947586
Palviainen M, Saraswat M, Varga Z et al (2020) Extracellular vesicles from human plasma and serum are carriers of extravesicular cargo-Implications for biomarker discovery. PLoS ONE 15:e236439
doi: 10.1371/journal.pone.0236439
pubmed: 32813744
pmcid: 7446890
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
doi: 10.1038/nature02871
pubmed: 15372042
Shu J, Silva B, Gao T et al (2017) Dynamic and Modularized MicroRNA Regulation and Its Implication in Human Cancers. Sci Rep 7:13356
doi: 10.1038/s41598-017-13470-5
pubmed: 29042600
pmcid: 5645395
Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114
doi: 10.1038/nrg2290
pubmed: 18197166
Yentrapalli R, Merl-Pham J, Azimzadeh O et al (2017) Quantitative changes in the protein and miRNA cargo of plasma exosome-like vesicles after exposure to ionizing radiation. Int J Radiat Biol 93:569–580
doi: 10.1080/09553002.2017.1294772
pubmed: 28264626
Szatmari T, Kis D, Bogdandi EN et al (2017) Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen. Front Immunol 8:347
doi: 10.3389/fimmu.2017.00347
pubmed: 28396668
pmcid: 5366932
Caivano A, La Rocca F, Simeon V et al (2017) MicroRNA-155 in serum-derived extracellular vesicles as a potential biomarker for hematologic malignancies—a short report. Cell Oncol (dordr) 40:97–103
doi: 10.1007/s13402-016-0300-x
pubmed: 27761889
Hehlgans S, Eke I, Deuse Y et al (2008) Integrin-linked kinase: dispensable for radiation survival of three-dimensionally cultured fibroblasts. Radiother Oncol 86:329–335
doi: 10.1016/j.radonc.2007.09.007
pubmed: 17905456
Brittain GCt CYQ, Martinez E et al (2019) A Novel Semiconductor-Based Flow Cytometer with Enhanced Light-Scatter Sensitivity for the Analysis of Biological Nanoparticles. Sci Rep 9:16039
doi: 10.1038/s41598-019-52366-4
Kanehisa M, Furumichi M, Tanabe M et al (2017) KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res 45:D353–D361
doi: 10.1093/nar/gkw1092
pubmed: 27899662
Heberle H, Meirelles GV, da Silva FR et al (2015) InteractiVenn: a web-based tool for the analysis of sets through Venn diagrams. BMC Bioinform 16:169
doi: 10.1186/s12859-015-0611-3
Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139–140
doi: 10.1093/bioinformatics/btp616
pubmed: 19910308
Wallace JA, O’Connell RM (2017) MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts. Blood 130:1290–1301
doi: 10.1182/blood-2016-10-697698
pubmed: 28751524
pmcid: 5600138
Aguilar-Hernandez MM, Rincon Camacho JC, Galicia Garcia G (2021) Extracellular vesicles and their associated miRNAs as potential prognostic biomarkers in chronic lymphocytic leukemia. Curr Oncol Rep 23:66
doi: 10.1007/s11912-021-01058-2
pubmed: 33855607
Liu T, Sun L, Ji Y et al (2024) Extracellular vesicles in cancer therapy: Roles, potential application, and challenges. Biochim Biophys Acta Rev Cancer 1879:189101
doi: 10.1016/j.bbcan.2024.189101
pubmed: 38608963
Abdelhamed S, Butler JT, Jung S et al (2021) Rational biomarker development for the early and minimally invasive monitoring of AML. Blood Adv 5:4515–4520
doi: 10.1182/bloodadvances.2021004621
pubmed: 34587228
pmcid: 8579272
Lin X, Ling Q, Lv Y et al (2020) Plasma exosome-derived microRNA-532 as a novel predictor for acute myeloid leukemia. Cancer Biomark 28:151–158
doi: 10.3233/CBM-191164
pubmed: 32176633
Heuser M, Freeman SD, Ossenkoppele GJ et al (2021) 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party. Blood 138:2753–2767
doi: 10.1182/blood.2021013626
pubmed: 34724563
pmcid: 8718623
Abou Dalle I, Labopin M, Kröger N et al (2023) Impact of disease burden on clinical outcomes of AML patients receiving allogeneic hematopoietic cell transplantation: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 58:784–790
doi: 10.1038/s41409-023-01961-1
pubmed: 37041215
Ganesan S, Palani HK, Lakshmanan V et al (2019) Stromal cells downregulate miR-23a-5p to activate protective autophagy in acute myeloid leukemia. Cell Death Dis 10:736
doi: 10.1038/s41419-019-1964-8
pubmed: 31570693
pmcid: 6769009
Naldini MM, Casirati G, Barcella M et al (2023) Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia. Nat Commun 14:1285
doi: 10.1038/s41467-023-36969-0
pubmed: 36890137
pmcid: 9995364
Chiba M, Monzen S, Iwaya C et al (2018) Serum miR-375-3p increase in mice exposed to a high dose of ionizing radiation. Sci Rep 8:1302
doi: 10.1038/s41598-018-19763-7
pubmed: 29358747
pmcid: 5778023
Brase JC, Johannes M, Schlomm T et al (2011) Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 128:608–616
doi: 10.1002/ijc.25376
pubmed: 20473869
Bouz Mkabaah L, Davey MG, Lennon JC et al (2023) Assessing the Role of MicroRNAs in Predicting Breast Cancer Recurrence—A Systematic Review. Int J Mol Sci 24:7115
Liu Y, Wang Q, Wen J et al (2021) MiR-375: A novel multifunctional regulator. Life Sci 275:119323
doi: 10.1016/j.lfs.2021.119323
pubmed: 33744323
Fan L, Li B, Li Z et al (2021) Identification of Autophagy Related circRNA-miRNA-mRNA-Subtypes Network With Radiotherapy Responses and Tumor Immune Microenvironment in Non-small Cell Lung Cancer. Front Genet 12:730003
doi: 10.3389/fgene.2021.730003
pubmed: 34567080
pmcid: 8458766
Kis D, Csordas IB, Persa E et al (2022) Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow. Cells 11:155
Pajic M, Froio D, Daly S et al (2018) miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing Multiple Gene Networks of DNA Repair and ROS Defense. Cancer Res 78:501–515
doi: 10.1158/0008-5472.CAN-16-3105
pubmed: 29180477