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Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA
The clonal evolution of acute myeloid leukemia (AML), an oligoclonal hematological malignancy, is driven by a plethora of cytogenetic abnormalities, gene mutations, abnormal epigenetic patterns, and aberrant gene expressions. These alterations in the leukemic blasts promote clinically diverse manife...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759522/ https://www.ncbi.nlm.nih.gov/pubmed/33363162 http://dx.doi.org/10.3389/fcell.2020.604391 |
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author | Thakral, Deepshi Gupta, Ritu Sahoo, Ranjit Kumar Verma, Pramod Kumar, Indresh Vashishtha, Sangeeta |
author_facet | Thakral, Deepshi Gupta, Ritu Sahoo, Ranjit Kumar Verma, Pramod Kumar, Indresh Vashishtha, Sangeeta |
author_sort | Thakral, Deepshi |
collection | PubMed |
description | The clonal evolution of acute myeloid leukemia (AML), an oligoclonal hematological malignancy, is driven by a plethora of cytogenetic abnormalities, gene mutations, abnormal epigenetic patterns, and aberrant gene expressions. These alterations in the leukemic blasts promote clinically diverse manifestations with common characteristics of high relapse and drug resistance. Defining and real-time monitoring of a personalized panel of these predictive genetic biomarkers is rapidly being adapted in clinical setting for diagnostic, prognostic, and therapeutic decision-making in AML. A major challenge remains the frequency of invasive biopsy procedures that can be routinely performed for monitoring of AML disease progression. Moreover, a single-site biopsy is not representative of the tumor heterogeneity as it is spatially and temporally constrained and necessitates the understanding of longitudinal and spatial subclonal dynamics in AML. Hematopoietic cells are a major contributor to plasma cell-free DNA, which also contain leukemia-specific aberrations as the circulating tumor-derived DNA (ctDNA) fraction. Plasma cell-free DNA analysis holds immense potential as a minimally invasive tool for genomic profiling at diagnosis as well as clonal evolution during AML disease progression. With the technological advances and increasing sensitivity for detection of ctDNA, both genetic and epigenetic aberrations can be qualitatively and quantitatively evaluated. However, challenges remain in validating the utility of liquid biopsy tools in clinics, and universal recommendations are still awaited towards reliable diagnostics and prognostics. Here, we provide an overview on the scope of ctDNA analyses for prognosis, assessment of response to treatment and measurable residual disease, prediction of disease relapse, development of acquired resistance and beyond in AML. |
format | Online Article Text |
id | pubmed-7759522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77595222020-12-26 Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA Thakral, Deepshi Gupta, Ritu Sahoo, Ranjit Kumar Verma, Pramod Kumar, Indresh Vashishtha, Sangeeta Front Cell Dev Biol Cell and Developmental Biology The clonal evolution of acute myeloid leukemia (AML), an oligoclonal hematological malignancy, is driven by a plethora of cytogenetic abnormalities, gene mutations, abnormal epigenetic patterns, and aberrant gene expressions. These alterations in the leukemic blasts promote clinically diverse manifestations with common characteristics of high relapse and drug resistance. Defining and real-time monitoring of a personalized panel of these predictive genetic biomarkers is rapidly being adapted in clinical setting for diagnostic, prognostic, and therapeutic decision-making in AML. A major challenge remains the frequency of invasive biopsy procedures that can be routinely performed for monitoring of AML disease progression. Moreover, a single-site biopsy is not representative of the tumor heterogeneity as it is spatially and temporally constrained and necessitates the understanding of longitudinal and spatial subclonal dynamics in AML. Hematopoietic cells are a major contributor to plasma cell-free DNA, which also contain leukemia-specific aberrations as the circulating tumor-derived DNA (ctDNA) fraction. Plasma cell-free DNA analysis holds immense potential as a minimally invasive tool for genomic profiling at diagnosis as well as clonal evolution during AML disease progression. With the technological advances and increasing sensitivity for detection of ctDNA, both genetic and epigenetic aberrations can be qualitatively and quantitatively evaluated. However, challenges remain in validating the utility of liquid biopsy tools in clinics, and universal recommendations are still awaited towards reliable diagnostics and prognostics. Here, we provide an overview on the scope of ctDNA analyses for prognosis, assessment of response to treatment and measurable residual disease, prediction of disease relapse, development of acquired resistance and beyond in AML. Frontiers Media S.A. 2020-12-11 /pmc/articles/PMC7759522/ /pubmed/33363162 http://dx.doi.org/10.3389/fcell.2020.604391 Text en Copyright © 2020 Thakral, Gupta, Sahoo, Verma, Kumar and Vashishtha. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Thakral, Deepshi Gupta, Ritu Sahoo, Ranjit Kumar Verma, Pramod Kumar, Indresh Vashishtha, Sangeeta Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA |
title | Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA |
title_full | Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA |
title_fullStr | Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA |
title_full_unstemmed | Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA |
title_short | Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA |
title_sort | real-time molecular monitoring in acute myeloid leukemia with circulating tumor dna |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759522/ https://www.ncbi.nlm.nih.gov/pubmed/33363162 http://dx.doi.org/10.3389/fcell.2020.604391 |
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