Chromosomal Instability in Acute Myeloid Leukemia
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...
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/11/2655 |
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| author | Mateus de Oliveira Lisboa Paulo Roberto Slud Brofman Ana Teresa Schmid-Braz Aline Rangel-Pozzo Sabine Mai |
| author_facet | Mateus de Oliveira Lisboa Paulo Roberto Slud Brofman Ana Teresa Schmid-Braz Aline Rangel-Pozzo Sabine Mai |
| author_sort | Mateus de Oliveira Lisboa |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:58:05Z |
| format | Article |
| id | doaj.art-f80f195f6cd74742a9b94b7f74ba03c1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:58:05Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f80f195f6cd74742a9b94b7f74ba03c12023-11-21T21:47:22ZengMDPI AGCancers2072-66942021-05-011311265510.3390/cancers13112655Chromosomal Instability in Acute Myeloid LeukemiaMateus de Oliveira Lisboa0Paulo Roberto Slud Brofman1Ana Teresa Schmid-Braz2Aline Rangel-Pozzo3Sabine Mai4Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná—PUCPR, Curitiba 80215-901, Paraná, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná—PUCPR, Curitiba 80215-901, Paraná, BrazilHospital das Clínicas, Universidade Federal do Paraná, Curitiba 80060-240, Paraná, BrazilDepartment of Physiology and Pathophysiology, University of Manitoba, Cell Biology, CancerCare Manitoba Research Institute, Winnipeg, MB R3C 2B7, CanadaDepartment of Physiology and Pathophysiology, University of Manitoba, Cell Biology, CancerCare Manitoba Research Institute, Winnipeg, MB R3C 2B7, CanadaChromosomal 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.https://www.mdpi.com/2072-6694/13/11/2655chromosomal instabilityacute myeloid leukemiacytogenetic heterogeneityaneuploidycomplex karyotype<i>TP53</i> |
| spellingShingle | Mateus de Oliveira Lisboa Paulo Roberto Slud Brofman Ana Teresa Schmid-Braz Aline Rangel-Pozzo Sabine Mai Chromosomal Instability in Acute Myeloid Leukemia Cancers chromosomal instability acute myeloid leukemia cytogenetic heterogeneity aneuploidy complex karyotype <i>TP53</i> |
| 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 | chromosomal instability acute myeloid leukemia cytogenetic heterogeneity aneuploidy complex karyotype <i>TP53</i> |
| url | https://www.mdpi.com/2072-6694/13/11/2655 |
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