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Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A

Relapse is associated with therapy resistance and is a major cause of death in acute myeloid leukemia (AML). It is thought to result from the accretion of therapy-refractory leukemic stem cells. Genetic and transcriptional changes that are recurrently gained at relapse are likely to contribute to th...

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Autores principales: Grandits, Alexander M., Wieser, Rotraud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612147/
https://www.ncbi.nlm.nih.gov/pubmed/34029637
http://dx.doi.org/10.1016/j.exphem.2021.05.004
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author Grandits, Alexander M.
Wieser, Rotraud
author_facet Grandits, Alexander M.
Wieser, Rotraud
author_sort Grandits, Alexander M.
collection PubMed
description Relapse is associated with therapy resistance and is a major cause of death in acute myeloid leukemia (AML). It is thought to result from the accretion of therapy-refractory leukemic stem cells. Genetic and transcriptional changes that are recurrently gained at relapse are likely to contribute to the increased stemness and decreased therapy responsiveness at this disease stage. Despite the recent approval of several targeted drugs, chemotherapy with cytosine arabinoside and anthracyclines is still the mainstay of AML therapy. Accordingly, a number of studies have investigated genetic and gene expression changes between diagnosis and relapse of patients subjected to such treatment. Genetic alterations recurrently acquired at relapse were identified, but were restricted to small proportions of patients, and their functional characterization is still largely pending. In contrast, the expression of a substantial number of genes was altered consistently between diagnosis and recurrence of AML. Recent studies corroborated the roles of the upregulation of SOCS2 and CALCRL and of the downregulation of MTSS1 and KDM6A in therapy resistance and/or stemness of AML. These findings spur the assumption that functional investigations of genes consistently altered at recurrence of AML have the potential to promote the development of novel targeted drugs that may help to improve the outcome of this currently often fatal disease.
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spelling pubmed-76121472022-01-03 Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A Grandits, Alexander M. Wieser, Rotraud Exp Hematol Article Relapse is associated with therapy resistance and is a major cause of death in acute myeloid leukemia (AML). It is thought to result from the accretion of therapy-refractory leukemic stem cells. Genetic and transcriptional changes that are recurrently gained at relapse are likely to contribute to the increased stemness and decreased therapy responsiveness at this disease stage. Despite the recent approval of several targeted drugs, chemotherapy with cytosine arabinoside and anthracyclines is still the mainstay of AML therapy. Accordingly, a number of studies have investigated genetic and gene expression changes between diagnosis and relapse of patients subjected to such treatment. Genetic alterations recurrently acquired at relapse were identified, but were restricted to small proportions of patients, and their functional characterization is still largely pending. In contrast, the expression of a substantial number of genes was altered consistently between diagnosis and recurrence of AML. Recent studies corroborated the roles of the upregulation of SOCS2 and CALCRL and of the downregulation of MTSS1 and KDM6A in therapy resistance and/or stemness of AML. These findings spur the assumption that functional investigations of genes consistently altered at recurrence of AML have the potential to promote the development of novel targeted drugs that may help to improve the outcome of this currently often fatal disease. 2021-07-01 2021-05-21 /pmc/articles/PMC7612147/ /pubmed/34029637 http://dx.doi.org/10.1016/j.exphem.2021.05.004 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Grandits, Alexander M.
Wieser, Rotraud
Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A
title Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A
title_full Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A
title_fullStr Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A
title_full_unstemmed Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A
title_short Gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of SOCS2, CALCRL, MTSS1, and KDM6A
title_sort gene expression changes contribute to stemness and therapy resistance of relapsed acute myeloid leukemia: roles of socs2, calcrl, mtss1, and kdm6a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612147/
https://www.ncbi.nlm.nih.gov/pubmed/34029637
http://dx.doi.org/10.1016/j.exphem.2021.05.004
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