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Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines

BACKGROUND: Hematological malignancies are a heterogeneous group of tumors with increased proliferative and auto-replicative capacity. Despite treatment advances, post-treatment quality of life remains highly affected. Studies addressing the molecular mechanisms of these diseases are critical for th...

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Autores principales: Alves, Jayse, Dexheimer, Georgia Muccillo, Reckzigel, Laura, Goettert, Marcia, Biolchi, Vanderlei, Abujamra, Ana Lucia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elmer Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153660/
https://www.ncbi.nlm.nih.gov/pubmed/32300452
http://dx.doi.org/10.14740/jh531
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author Alves, Jayse
Dexheimer, Georgia Muccillo
Reckzigel, Laura
Goettert, Marcia
Biolchi, Vanderlei
Abujamra, Ana Lucia
author_facet Alves, Jayse
Dexheimer, Georgia Muccillo
Reckzigel, Laura
Goettert, Marcia
Biolchi, Vanderlei
Abujamra, Ana Lucia
author_sort Alves, Jayse
collection PubMed
description BACKGROUND: Hematological malignancies are a heterogeneous group of tumors with increased proliferative and auto-replicative capacity. Despite treatment advances, post-treatment quality of life remains highly affected. Studies addressing the molecular mechanisms of these diseases are critical for the development of effective, rapid and selective therapies, since few therapeutic strategies succeed in being effective without triggering high-grade toxicities or debilitating late effects. Our aim of this study was to verify changes in the expression of genes involved in the malignant phenotype of hematological malignancies, by treating human cell lines in vitro with classic chemotherapeutic agents and the demethylating agent, decitabine. METHODS: KASUMI-1 and K-562 human myeloid leukemia cell lines were plated at a density of 3 × 10(4) cells/well and treated with increasing concentrations of different chemotherapeutic agents commonly used in the clinical setting. After 24 and 48 h of treatment, cell viability was tested, and RNA was extracted. Complementary DNA (cDNA) was synthesized and quantitative real-time polymerase chain reaction (qPCR) was performed to evaluate the gene expression of IDH2, TET2 and KDM2B. RESULTS: A modulation in gene expression was observed before and after treatment with classic chemotherapeutic agents. It was possible to demonstrate a difference in gene expression when cells were treated with chemotherapeutic agents or decitabine alone when compared to chemotherapeutic agents in association with decitabine. CONCLUSIONS: The genes tested, and the modulation of their expression during in vitro treatments suggest that IDH2, TET2, and KDM2B should be further investigated as potential biomarkers for ongoing treatment response and follow-up for patients diagnosed with hematological malignancies of the myeloid lineage.
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spelling pubmed-71536602020-04-16 Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines Alves, Jayse Dexheimer, Georgia Muccillo Reckzigel, Laura Goettert, Marcia Biolchi, Vanderlei Abujamra, Ana Lucia J Hematol Original Article BACKGROUND: Hematological malignancies are a heterogeneous group of tumors with increased proliferative and auto-replicative capacity. Despite treatment advances, post-treatment quality of life remains highly affected. Studies addressing the molecular mechanisms of these diseases are critical for the development of effective, rapid and selective therapies, since few therapeutic strategies succeed in being effective without triggering high-grade toxicities or debilitating late effects. Our aim of this study was to verify changes in the expression of genes involved in the malignant phenotype of hematological malignancies, by treating human cell lines in vitro with classic chemotherapeutic agents and the demethylating agent, decitabine. METHODS: KASUMI-1 and K-562 human myeloid leukemia cell lines were plated at a density of 3 × 10(4) cells/well and treated with increasing concentrations of different chemotherapeutic agents commonly used in the clinical setting. After 24 and 48 h of treatment, cell viability was tested, and RNA was extracted. Complementary DNA (cDNA) was synthesized and quantitative real-time polymerase chain reaction (qPCR) was performed to evaluate the gene expression of IDH2, TET2 and KDM2B. RESULTS: A modulation in gene expression was observed before and after treatment with classic chemotherapeutic agents. It was possible to demonstrate a difference in gene expression when cells were treated with chemotherapeutic agents or decitabine alone when compared to chemotherapeutic agents in association with decitabine. CONCLUSIONS: The genes tested, and the modulation of their expression during in vitro treatments suggest that IDH2, TET2, and KDM2B should be further investigated as potential biomarkers for ongoing treatment response and follow-up for patients diagnosed with hematological malignancies of the myeloid lineage. Elmer Press 2019-09 2019-09-30 /pmc/articles/PMC7153660/ /pubmed/32300452 http://dx.doi.org/10.14740/jh531 Text en Copyright 2019, Alves et al. http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Alves, Jayse
Dexheimer, Georgia Muccillo
Reckzigel, Laura
Goettert, Marcia
Biolchi, Vanderlei
Abujamra, Ana Lucia
Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines
title Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines
title_full Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines
title_fullStr Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines
title_full_unstemmed Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines
title_short Changes in IDH2, TET2 and KDM2B Gene Expression After Treatment With Classic Chemotherapeutic Agents and Decitabine in Myelogenous Leukemia Cell Lines
title_sort changes in idh2, tet2 and kdm2b gene expression after treatment with classic chemotherapeutic agents and decitabine in myelogenous leukemia cell lines
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153660/
https://www.ncbi.nlm.nih.gov/pubmed/32300452
http://dx.doi.org/10.14740/jh531
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