TY - JOUR
T1 - Biomarkers in Acute Myeloid Leukemia
T2 - Leveraging Next Generation Sequencing Data for Optimal Therapeutic Strategies
AU - El Achi, Hanadi
AU - Kanagal-Shamanna, Rashmi
N1 - Publisher Copyright:
© Copyright © 2021 El Achi and Kanagal-Shamanna.
PY - 2021/9/30
Y1 - 2021/9/30
N2 - Next generation sequencing (NGS) is routinely used for mutation profiling of acute myeloid leukemia. The extensive application of NGS in hematologic malignancies, and its significant association with the outcomes in multiple large cohorts constituted a proof of concept that AML phenotype is driven by underlying mutational signature and is amenable for targeted therapies. These findings urged incorporation of molecular results into the latest World Health Organization (WHO) sub-classification and integration into risk-stratification and treatment guidelines by the European Leukemia Net. NGS mutation profiling provides a large amount of information that guides diagnosis and management, dependent on the type and number of gene mutations, variant allele frequency and amenability to targeted therapeutics. Hence, molecular mutational profiling is an integral component for work-up of AML and multiple leukemic entities. In addition, there is a vast amount of informative data that can be obtained from routine clinical NGS sequencing beyond diagnosis, prognostication and therapeutic targeting. These include identification of evidence regarding the ontogeny of the disease, underlying germline predisposition and clonal hematopoiesis, serial monitoring to assess the effectiveness of therapy and resistance mutations, which have broader implications for management. In this review, using a few prototypic genes in AML, we will summarize the clinical applications of NGS generated data for optimal AML management, with emphasis on the recently described entities and Food and Drug Administration approved target therapies.
AB - Next generation sequencing (NGS) is routinely used for mutation profiling of acute myeloid leukemia. The extensive application of NGS in hematologic malignancies, and its significant association with the outcomes in multiple large cohorts constituted a proof of concept that AML phenotype is driven by underlying mutational signature and is amenable for targeted therapies. These findings urged incorporation of molecular results into the latest World Health Organization (WHO) sub-classification and integration into risk-stratification and treatment guidelines by the European Leukemia Net. NGS mutation profiling provides a large amount of information that guides diagnosis and management, dependent on the type and number of gene mutations, variant allele frequency and amenability to targeted therapeutics. Hence, molecular mutational profiling is an integral component for work-up of AML and multiple leukemic entities. In addition, there is a vast amount of informative data that can be obtained from routine clinical NGS sequencing beyond diagnosis, prognostication and therapeutic targeting. These include identification of evidence regarding the ontogeny of the disease, underlying germline predisposition and clonal hematopoiesis, serial monitoring to assess the effectiveness of therapy and resistance mutations, which have broader implications for management. In this review, using a few prototypic genes in AML, we will summarize the clinical applications of NGS generated data for optimal AML management, with emphasis on the recently described entities and Food and Drug Administration approved target therapies.
KW - actionable mutations
KW - acute myeloid leukemia
KW - AML
KW - FDA
KW - next generation sequencing
KW - targeted therapy
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U2 - 10.3389/fonc.2021.748250
DO - 10.3389/fonc.2021.748250
M3 - Review article
C2 - 34660311
AN - SCOPUS:85117150292
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 748250
ER -