ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia
| Autor: | Baykal-Köse S; İzmir Biomedicine and Genome Center, İzmir, Türkiye; Dokuz Eylül University Faculty of Medicine, Department of Medical Biology, İzmir, Türkiye, Voldoire M; CHD La Roche-sur-Yon-Service de Médecine Onco-Hématologie, La Roche-sur-Yon, Pays de la Loire, France, Desterke C; Université Paris-Saclay BU Kremlin-Bicêtre-Faculté de Médecine, Le Kremlin-Bicetre, Île-de-France, Sorel N; CHU Poitiers-Service de Cancérologie Biologique, Poitiers, France, Cayssials E; CHU Poitiers-Service d’Oncologie Hématologique et Thérapie Cellulaire, Poitiers, France, Johnson-Ansah H; CHRU de Caen-Service d'Hématologie Clinique, Caen, Basse-Normandie, France, Guerci-Bresler A; Hôpital Brabois-Service d'Hématologie Clinique, Vandoeuvre les Nancy, France, Bennaceur-Griscelli A; AP-HP Université Paris Saclay-Service d’Hématologie, Le Kremlin-Bicetre, Île-de-France, France, Chomel JC; INSERM-UA9, Villejuif, Paris, Île-de-France, France, Turhan AG; Paris-Saclay University-Service d'hematologie, Hopital Bicetre, Paris, Villejuif, France |
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| Jazyk: | angličtina |
| Zdroj: | Turkish journal of haematology : official journal of Turkish Society of Haematology [Turk J Haematol] 2023 May 29; Vol. 40 (2), pp. 101-117. Date of Electronic Publication: 2023 Apr 07. |
| DOI: | 10.4274/tjh.galenos.2023.2022-0339 |
| Abstrakt: | 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. Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors. (©Copyright 2023 by Turkish Society of Hematology | Turkish Journal of Hematology, Published by Galenos Publishing House) |
| Databáze: | MEDLINE |
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