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Chromosomal Instability in Acute Myeloid Leukemia

SIMPLE SUMMARY: Chromosome instability (CIN) is an increased rate where chromosome acquire alterations due to errors in cell division. CIN creates genetic and cytogenetic diversity and is a common feature in hematological malignancies such as acute myeloid leukemia (AML). Low to moderate levels of C...

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Autores principales: de Oliveira Lisboa, Mateus, Brofman, Paulo Roberto Slud, Schmid-Braz, Ana Teresa, Rangel-Pozzo, Aline, Mai, Sabine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198625/
https://www.ncbi.nlm.nih.gov/pubmed/34071283
http://dx.doi.org/10.3390/cancers13112655
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author de Oliveira Lisboa, Mateus
Brofman, Paulo Roberto Slud
Schmid-Braz, Ana Teresa
Rangel-Pozzo, Aline
Mai, Sabine
author_facet de Oliveira Lisboa, Mateus
Brofman, Paulo Roberto Slud
Schmid-Braz, Ana Teresa
Rangel-Pozzo, Aline
Mai, Sabine
author_sort de Oliveira Lisboa, Mateus
collection PubMed
description SIMPLE SUMMARY: Chromosome instability (CIN) is an increased rate where chromosome acquire alterations due to errors in cell division. CIN creates genetic and cytogenetic diversity and is a common feature in hematological malignancies such as acute myeloid leukemia (AML). Low to moderate levels of CIN seems to be well tolerated and can promote cancer proliferation, genetic diversity, and tumor evolution. However, high levels of CIN seems to be lethal, where enhancing CIN could improve AML treatment. However, little is known about CIN in AML. Our review focus on CIN studies in AML, their prognostic results, as well as the use of CIN as a therapeutic target in AML. ABSTRACT: Chromosomal instability (CIN), the increasing rate in which cells acquire new chromosomal alterations, is one of the hallmarks of cancer. Many studies highlighted CIN as an important mechanism in the origin, progression, and relapse of acute myeloid leukemia (AML). The ambivalent feature of CIN as a cancer-promoting or cancer-suppressing mechanism might explain the prognostic variability. The latter, however, is described in very few studies. This review highlights the important CIN mechanisms in AML, showing that CIN signatures can occur largely in all the three major AML types (de novo AML, secondary-AML, and therapy-related-AML). CIN features in AML could also be age-related and reflect the heterogeneity of the disease. Although most of these abnormalities show an adverse prognostic value, they also offer a strong new perspective on personalized therapy approaches, which goes beyond assessing CIN in vitro in patient tumor samples to predict prognosis. Current and emerging AML therapies are exploring CIN to improve AML treatment, which includes blocking CIN or increasing CIN beyond the limit threshold to induce cell death. We argue that the characterization of CIN features, not included yet in the routine diagnostic of AML patients, might provide a better stratification of patients and be extended to a more personalized therapeutic approach.
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spelling pubmed-81986252021-06-14 Chromosomal Instability in Acute Myeloid Leukemia de Oliveira Lisboa, Mateus Brofman, Paulo Roberto Slud Schmid-Braz, Ana Teresa Rangel-Pozzo, Aline Mai, Sabine Cancers (Basel) Review SIMPLE SUMMARY: Chromosome instability (CIN) is an increased rate where chromosome acquire alterations due to errors in cell division. CIN creates genetic and cytogenetic diversity and is a common feature in hematological malignancies such as acute myeloid leukemia (AML). Low to moderate levels of CIN seems to be well tolerated and can promote cancer proliferation, genetic diversity, and tumor evolution. However, high levels of CIN seems to be lethal, where enhancing CIN could improve AML treatment. However, little is known about CIN in AML. Our review focus on CIN studies in AML, their prognostic results, as well as the use of CIN as a therapeutic target in AML. ABSTRACT: Chromosomal instability (CIN), the increasing rate in which cells acquire new chromosomal alterations, is one of the hallmarks of cancer. Many studies highlighted CIN as an important mechanism in the origin, progression, and relapse of acute myeloid leukemia (AML). The ambivalent feature of CIN as a cancer-promoting or cancer-suppressing mechanism might explain the prognostic variability. The latter, however, is described in very few studies. This review highlights the important CIN mechanisms in AML, showing that CIN signatures can occur largely in all the three major AML types (de novo AML, secondary-AML, and therapy-related-AML). CIN features in AML could also be age-related and reflect the heterogeneity of the disease. Although most of these abnormalities show an adverse prognostic value, they also offer a strong new perspective on personalized therapy approaches, which goes beyond assessing CIN in vitro in patient tumor samples to predict prognosis. Current and emerging AML therapies are exploring CIN to improve AML treatment, which includes blocking CIN or increasing CIN beyond the limit threshold to induce cell death. We argue that the characterization of CIN features, not included yet in the routine diagnostic of AML patients, might provide a better stratification of patients and be extended to a more personalized therapeutic approach. MDPI 2021-05-28 /pmc/articles/PMC8198625/ /pubmed/34071283 http://dx.doi.org/10.3390/cancers13112655 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
de Oliveira Lisboa, Mateus
Brofman, Paulo Roberto Slud
Schmid-Braz, Ana Teresa
Rangel-Pozzo, Aline
Mai, Sabine
Chromosomal Instability in Acute Myeloid Leukemia
title Chromosomal Instability in Acute Myeloid Leukemia
title_full Chromosomal Instability in Acute Myeloid Leukemia
title_fullStr Chromosomal Instability in Acute Myeloid Leukemia
title_full_unstemmed Chromosomal Instability in Acute Myeloid Leukemia
title_short Chromosomal Instability in Acute Myeloid Leukemia
title_sort chromosomal instability in acute myeloid leukemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198625/
https://www.ncbi.nlm.nih.gov/pubmed/34071283
http://dx.doi.org/10.3390/cancers13112655
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