ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia
Objective: Chronic myeloid leukemia (CML) is a disease caused by the acquisition of BCR-ABL1 fusion in hematopoietic stem cells. In this study, we focus on the oncofetal ENOX2 protein as a potential secretable biomarker in CML. Materials and Methods: We used cell culture, western blot, quantitative...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Galenos Publishing House
2023-06-01
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| Series: | Turkish Journal of Hematology |
| Subjects: | |
| Online Access: | https://tjh.com.tr/jvi.aspx?pdir=tjh&plng=eng&un=TJH-21447&look4= |
| _version_ | 1797813563407990784 |
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| author | Seda Baykal Maud Voldoire Christophe Desterke Nathalie Sorel Emilie Cayssials Hyacinthe Johnson-Ansah Agnes Guerci-Bresler Annelise Bennaceur-Griscelli Jean-Claude Chome Ali G. Turhan |
| author_facet | Seda Baykal Maud Voldoire Christophe Desterke Nathalie Sorel Emilie Cayssials Hyacinthe Johnson-Ansah Agnes Guerci-Bresler Annelise Bennaceur-Griscelli Jean-Claude Chome Ali G. Turhan |
| author_sort | Seda Baykal |
| collection | DOAJ |
| description | Objective: Chronic myeloid leukemia (CML) is a disease caused by the acquisition of BCR-ABL1 fusion in hematopoietic stem cells. In this study, we focus on the oncofetal ENOX2 protein as a potential secretable biomarker in CML.
Materials and Methods: We used cell culture, western blot, quantitative RT-PCR, ELISA, transcriptome analyses, and bioinformatics techniques to investigate ENOX2 mRNA and protein expression.
Results: Western blot analyses of UT-7 and TET-inducible Ba/F3 cell lines demonstrated the upregulation of the ENOX2 protein. BCR-ABL1 was found to induce ENOX2 overexpression in a kinase-dependent manner. We confirmed increased ENOX2 mRNA expression in a cohort of CML patients at diagnosis. In a series of CML patients, ELISA assays showed a highly significant increase of ENOX2 protein levels in the plasma of patients with CML compared to controls. Reanalyzing the transcriptomic dataset confirmed ENOX2 mRNA overexpression in the chronic phase of the disease. Bioinformatic analyses identified several genes whose mRNA expressions were positively correlated with ENOX2 in the context of BCR-ABL1. Some of them encode proteins involved in cellular functions compatible with the growth deregulation observed in CML.
Conclusion: Our results highlight the upregulation of a secreted redox protein in a BCR-ABL1-dependent manner in CML. The data presented here suggest that ENOX2, through its transcriptional mechanism, plays a significant role in BCR-ABL1 leukemogenesis. |
| first_indexed | 2024-03-13T07:54:36Z |
| format | Article |
| id | doaj.art-f24131ac61f244a59ac5e89c9052cb12 |
| institution | Directory Open Access Journal |
| issn | 1308-5263 |
| language | English |
| last_indexed | 2024-03-13T07:54:36Z |
| publishDate | 2023-06-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Turkish Journal of Hematology |
| spelling | doaj.art-f24131ac61f244a59ac5e89c9052cb122023-06-02T08:37:42ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632023-06-0140210111710.4274/tjh.galenos.2023.2022-0339ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid LeukemiaSeda Baykal0https://orcid.org/0000-0001-8654-5332Maud Voldoire1Christophe Desterke2Nathalie Sorel3Emilie Cayssials4Hyacinthe Johnson-Ansah5Agnes Guerci-Bresler6Annelise Bennaceur-Griscelli7Jean-Claude Chome8Ali G. Turhan9https://orcid.org/0000-0002-4861-0137İzmir Biomedicine and Genome Center, İzmir, Türkiye; Dokuz Eylül University Faculty of Medicine, Department of Medical Biology, İzmir, TürkiyeCHD La Roche-sur-Yon-Service de Médecine Onco-Hématologie, La Roche-sur-Yon, Pays de la Loire, FranceUniversité Paris-Saclay BU Kremlin-Bicêtre-Faculté de Médecine, Le Kremlin-Bicetre, Île-de-FranceCHU Poitiers-Service de Cancérologie Biologique, Poitiers, FranceCHU Poitiers-Service d’Oncologie Hématologique et Thérapie Cellulaire, Poitiers, FranceCHRU de Caen-Service d'Hématologie Clinique, Caen, Basse-Normandie, France Hôpital Brabois-Service d'Hématologie Clinique, Vandoeuvre les Nancy, FranceAP-HP Université Paris Saclay-Service d’Hématologie, Le Kremlin-Bicetre, Île-de-France, FranceINSERM-UA9, Villejuif, Paris, Île-de-France, FranceParis-Saclay University-Service d'hematologie, Hopital Bicetre, Paris, Villejuif, FranceObjective: Chronic myeloid leukemia (CML) is a disease caused by the acquisition of BCR-ABL1 fusion in hematopoietic stem cells. In this study, we focus on the oncofetal ENOX2 protein as a potential secretable biomarker in CML. Materials and Methods: We used cell culture, western blot, quantitative RT-PCR, ELISA, transcriptome analyses, and bioinformatics techniques to investigate ENOX2 mRNA and protein expression. Results: Western blot analyses of UT-7 and TET-inducible Ba/F3 cell lines demonstrated the upregulation of the ENOX2 protein. BCR-ABL1 was found to induce ENOX2 overexpression in a kinase-dependent manner. We confirmed increased ENOX2 mRNA expression in a cohort of CML patients at diagnosis. In a series of CML patients, ELISA assays showed a highly significant increase of ENOX2 protein levels in the plasma of patients with CML compared to controls. Reanalyzing the transcriptomic dataset confirmed ENOX2 mRNA overexpression in the chronic phase of the disease. Bioinformatic analyses identified several genes whose mRNA expressions were positively correlated with ENOX2 in the context of BCR-ABL1. Some of them encode proteins involved in cellular functions compatible with the growth deregulation observed in CML. Conclusion: Our results highlight the upregulation of a secreted redox protein in a BCR-ABL1-dependent manner in CML. The data presented here suggest that ENOX2, through its transcriptional mechanism, plays a significant role in BCR-ABL1 leukemogenesis.https://tjh.com.tr/jvi.aspx?pdir=tjh&plng=eng&un=TJH-21447&look4=cmlenox2biomarkerchronic myeloid leukemiaredox proteinsecreted protein |
| spellingShingle | Seda Baykal Maud Voldoire Christophe Desterke Nathalie Sorel Emilie Cayssials Hyacinthe Johnson-Ansah Agnes Guerci-Bresler Annelise Bennaceur-Griscelli Jean-Claude Chome Ali G. Turhan ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia Turkish Journal of Hematology cml enox2 biomarker chronic myeloid leukemia redox protein secreted protein |
| title | ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia |
| title_full | ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia |
| title_fullStr | ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia |
| title_full_unstemmed | ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia |
| title_short | ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia |
| title_sort | enox2 nadh oxidase a bcr abl1 dependent cell surface and secreted redox protein in chronic myeloid leukemia |
| topic | cml enox2 biomarker chronic myeloid leukemia redox protein secreted protein |
| url | https://tjh.com.tr/jvi.aspx?pdir=tjh&plng=eng&un=TJH-21447&look4= |
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