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The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis

BACKGROUND: The underlying mechanism of myeloid malignancies like myelodysplastic syndrome (MDS) and acute myelocytic leukemia (AML) with bone marrow (BM) fibrosis (hereafter referred to as MDS-F and AML-F) is not fully understood. This study aimed to investigate the role of the E3 protein ubiquitin...

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Autores principales: Han, Shuang, Zhang, Yao, Guo, Cha, Chang, Chunkang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797868/
https://www.ncbi.nlm.nih.gov/pubmed/35116552
http://dx.doi.org/10.21037/tcr-20-3115
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author Han, Shuang
Zhang, Yao
Guo, Cha
Chang, Chunkang
author_facet Han, Shuang
Zhang, Yao
Guo, Cha
Chang, Chunkang
author_sort Han, Shuang
collection PubMed
description BACKGROUND: The underlying mechanism of myeloid malignancies like myelodysplastic syndrome (MDS) and acute myelocytic leukemia (AML) with bone marrow (BM) fibrosis (hereafter referred to as MDS-F and AML-F) is not fully understood. This study aimed to investigate the role of the E3 protein ubiquitin ligase Itch in the pathogenesis of these diseases preliminarily. METHODS: Through bioinformatic methods we found that the E3 protein ubiquitin ligase Itch might play a role in the pathogenesis of MDS-F and AML-F as well as the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. We first investigated whether the PI3K/Akt pathway could regulate the expression Itch and its substrate p73 by using the myeloid neoplasm cell line K562 as a model. Then we assayed the Itch mRNA level of clinical samples in different subgroups to have a knowledge of its role in the myeloid diseases. RESULTS: Through the cellular experiments we got that the PI3K/Akt pathway might not regulate the expression of Itch and its substrate p73. In patients with high risk MDS, AML, fibrosis or higher white blood cells (WBC) count, Itch mRNA level significantly increased when compared with the control groups. But the mRNA level didn’t show significant difference in the subgroups classified by karyotype. Through correlative analysis we found that the mRNA level had positive correlation with the WBC count of the patients. CONCLUSIONS: The PI3K/Akt pathway may not get involved in the regulation of the expression of Itch in K562 cells or myeloid tumors and Itch may play a role both in the proliferation and the generation of fibrosis in myeloid malignancies.
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spelling pubmed-87978682022-02-02 The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis Han, Shuang Zhang, Yao Guo, Cha Chang, Chunkang Transl Cancer Res Original Article BACKGROUND: The underlying mechanism of myeloid malignancies like myelodysplastic syndrome (MDS) and acute myelocytic leukemia (AML) with bone marrow (BM) fibrosis (hereafter referred to as MDS-F and AML-F) is not fully understood. This study aimed to investigate the role of the E3 protein ubiquitin ligase Itch in the pathogenesis of these diseases preliminarily. METHODS: Through bioinformatic methods we found that the E3 protein ubiquitin ligase Itch might play a role in the pathogenesis of MDS-F and AML-F as well as the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. We first investigated whether the PI3K/Akt pathway could regulate the expression Itch and its substrate p73 by using the myeloid neoplasm cell line K562 as a model. Then we assayed the Itch mRNA level of clinical samples in different subgroups to have a knowledge of its role in the myeloid diseases. RESULTS: Through the cellular experiments we got that the PI3K/Akt pathway might not regulate the expression of Itch and its substrate p73. In patients with high risk MDS, AML, fibrosis or higher white blood cells (WBC) count, Itch mRNA level significantly increased when compared with the control groups. But the mRNA level didn’t show significant difference in the subgroups classified by karyotype. Through correlative analysis we found that the mRNA level had positive correlation with the WBC count of the patients. CONCLUSIONS: The PI3K/Akt pathway may not get involved in the regulation of the expression of Itch in K562 cells or myeloid tumors and Itch may play a role both in the proliferation and the generation of fibrosis in myeloid malignancies. AME Publishing Company 2021-05 /pmc/articles/PMC8797868/ /pubmed/35116552 http://dx.doi.org/10.21037/tcr-20-3115 Text en 2021 Translational Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Original Article
Han, Shuang
Zhang, Yao
Guo, Cha
Chang, Chunkang
The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis
title The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis
title_full The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis
title_fullStr The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis
title_full_unstemmed The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis
title_short The E3 protein ubiquitin ligase Itch is a potential target in myeloid malignancies with marrow fibrosis
title_sort e3 protein ubiquitin ligase itch is a potential target in myeloid malignancies with marrow fibrosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797868/
https://www.ncbi.nlm.nih.gov/pubmed/35116552
http://dx.doi.org/10.21037/tcr-20-3115
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