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Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers

Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while ty...

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Autores principales: Krishnan, Vaidehi, Kim, Dennis Dong Hwan, Hughes, Timothy P., Branford, Susan, Ong, S. Tiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804571/
https://www.ncbi.nlm.nih.gov/pubmed/34615339
http://dx.doi.org/10.3324/haematol.2021.279317
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author Krishnan, Vaidehi
Kim, Dennis Dong Hwan
Hughes, Timothy P.
Branford, Susan
Ong, S. Tiong
author_facet Krishnan, Vaidehi
Kim, Dennis Dong Hwan
Hughes, Timothy P.
Branford, Susan
Ong, S. Tiong
author_sort Krishnan, Vaidehi
collection PubMed
description Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while tyrosine kinase inhibitor therapy is the standard treatment, current clinical scoring systems cannot accurately predict the heterogeneous treatment outcomes observed in patients. Biomarkers capable of segregating patients according to outcome at diagnosis are needed to improve management, and facilitate enrollment in clinical trials seeking to prevent blast crisis transformation and improve the depth of molecular responses. To this end, gene expression (GE) profiling studies have evaluated whether GE signatures at diagnosis are clinically informative. Patient material from a variety of sources has been profiled using microarrays, RNA sequencing and, more recently, single-cell RNA sequencing. However, differences in the cell types profiled, the technologies used, and the inherent complexities associated with the interpretation of genomic data pose challenges in distilling GE datasets into biomarkers with clinical utility. The goal of this paper is to review previous studies evaluating GE profiling in CML, and explore their potential as risk assessment tools for individualized CML treatment. We also review the contribution that acquired mutations, including those seen in clonal hematopoiesis, make to GE profiles, and how a model integrating contributions of genetic and epigenetic factors in resistance to tyrosine kinase inhibitors and blast crisis transformation can define a route to GE-based biomarkers. Finally, we outline a four-stage approach for the development of GE-based biomarkers in CML.
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spelling pubmed-88045712022-02-23 Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers Krishnan, Vaidehi Kim, Dennis Dong Hwan Hughes, Timothy P. Branford, Susan Ong, S. Tiong Haematologica Review Article Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while tyrosine kinase inhibitor therapy is the standard treatment, current clinical scoring systems cannot accurately predict the heterogeneous treatment outcomes observed in patients. Biomarkers capable of segregating patients according to outcome at diagnosis are needed to improve management, and facilitate enrollment in clinical trials seeking to prevent blast crisis transformation and improve the depth of molecular responses. To this end, gene expression (GE) profiling studies have evaluated whether GE signatures at diagnosis are clinically informative. Patient material from a variety of sources has been profiled using microarrays, RNA sequencing and, more recently, single-cell RNA sequencing. However, differences in the cell types profiled, the technologies used, and the inherent complexities associated with the interpretation of genomic data pose challenges in distilling GE datasets into biomarkers with clinical utility. The goal of this paper is to review previous studies evaluating GE profiling in CML, and explore their potential as risk assessment tools for individualized CML treatment. We also review the contribution that acquired mutations, including those seen in clonal hematopoiesis, make to GE profiles, and how a model integrating contributions of genetic and epigenetic factors in resistance to tyrosine kinase inhibitors and blast crisis transformation can define a route to GE-based biomarkers. Finally, we outline a four-stage approach for the development of GE-based biomarkers in CML. Fondazione Ferrata Storti 2021-10-07 /pmc/articles/PMC8804571/ /pubmed/34615339 http://dx.doi.org/10.3324/haematol.2021.279317 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Review Article
Krishnan, Vaidehi
Kim, Dennis Dong Hwan
Hughes, Timothy P.
Branford, Susan
Ong, S. Tiong
Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
title Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
title_full Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
title_fullStr Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
title_full_unstemmed Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
title_short Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
title_sort integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804571/
https://www.ncbi.nlm.nih.gov/pubmed/34615339
http://dx.doi.org/10.3324/haematol.2021.279317
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