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Medientyp:
E-Artikel
Titel:
Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers
Beteiligte:
Krishnan, Vaidehi;
Kim, Dennis Dong Hwan;
Hughes, Timothy P.;
Branford, Susan;
Ong, S. Tiong
Erschienen:
Ferrata Storti Foundation (Haematologica), 2021
Erschienen in:
Haematologica, 107 (2021) 2, Seite 358-370
Sprache:
Nicht zu entscheiden
DOI:
10.3324/haematol.2021.279317
ISSN:
0390-6078;
1592-8721
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>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.</jats:p>