Dataset Information

When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter.

ABSTRACT: Mutational profiling has fundamentally changed our approach to patients with acute myeloid leukemia (AML). Patients with AML are routinely profiled for the presence of mutations in FLT3, NPM1, CEBPA, and, more recently, TP53 In this chapter, we review the role of mutational profiling to help define disease biology in AML, particularly among patients with putatively intermediate-risk disease. We describe the body of evidence supporting the utility of mutational profiling when performed at the time of diagnosis (to identify prognostic and targetable mutations), at the time of complete remission (to assess minimal residual disease as a marker for relapse), and at the time of relapse (to identify therapeutic targets and eligibility for clinical trials). We further identify particular mutations that have been shown to affect prognosis across the established European LeukemiaNet risk categories and discuss which mutational events might be used to alter the approach to patient care at various time points during the disease course. We also review the evidence in support of molecular profiling for assessment of minimal/measurable residual disease and describe the current landscape of studies designed to validate this approach.

SUBMITTER: Roloff GW

PROVIDER: S-EPMC6234366 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter.

Roloff Gregory W GW Griffiths Elizabeth A EA

Blood advances 20181101 21

Mutational profiling has fundamentally changed our approach to patients with acute myeloid leukemia (AML). Patients with AML are routinely profiled for the presence of mutations in FLT3, NPM1, CEBPA, and, more recently, TP53 In this chapter, we review the role of mutational profiling to help define disease biology in AML, particularly among patients with putatively intermediate-risk disease. We describe the body of evidence supporting the utility of mutational profili ...[more]

PMID: 30425072

Similar Datasets

Project description:The last two decades of genome-scale research revealed a complex molecular picture of acute myeloid leukemia (AML). On the one hand, a number of mutations were discovered and associated with AML diagnosis and prognosis; some of them were introduced into diagnostic tests. On the other hand, transcriptome studies, which preceded AML exome and genome sequencing, remained poorly translated into clinics. Nevertheless, gene expression studies significantly contributed to the elucidation of AML pathogenesis and indicated potential therapeutic directions. The power of transcriptomic approach lies in its comprehensiveness; we can observe how genome manifests its function in a particular type of cells and follow many genes in one test. Moreover, gene expression measurement can be combined with mutation detection, as high-impact mutations are often present in transcripts. This review sums up 20 years of transcriptome research devoted to AML. Gene expression profiling (GEP) revealed signatures distinctive for selected AML subtypes and uncovered the additional within-subtype heterogeneity. The results were particularly valuable in the case of AML with normal karyotype which concerns up to 50% of AML cases. With the use of GEP, new classes of the disease were identified and prognostic predictors were proposed. A plenty of genes were detected as overexpressed in AML when compared to healthy control, including KIT, BAALC, ERG, MN1, CDX2, WT1, PRAME, and HOX genes. High expression of these genes constitutes usually an unfavorable prognostic factor. Upregulation of FLT3 and NPM1 genes, independent on their mutation status, was also reported in AML and correlated with poor outcome. However, transcriptome is not limited to the protein-coding genes; other types of RNA molecules exist in a cell and regulate genome function. It was shown that microRNA (miRNA) profiles differentiated AML groups and predicted outcome not worse than protein-coding gene profiles. For example, upregulation of miR-10a, miR-10b, and miR-196b and downregulation of miR-192 were found as typical of AML with NPM1 mutation whereas overexpression of miR-155 was associated with FLT3-internal tandem duplication (FLT3-ITD). Development of high-throughput technologies and microarray replacement by next generation sequencing (RNA-seq) enabled uncovering a real variety of leukemic cell transcriptomes, reflected by gene fusions, chimeric RNAs, alternatively spliced transcripts, miRNAs, piRNAs, long noncoding RNAs (lncRNAs), and their special type, circular RNAs. Many of them can be considered as AML biomarkers and potential therapeutic targets. The relations between particular RNA puzzles and other components of leukemic cells and their microenvironment, such as exosomes, are now under investigation. Hopefully, the results of this research will shed the light on these aspects of AML pathogenesis which are still not completely understood.

Dataset Information

When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter.

Publications

When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets