Targeted RNA-sequencing for the quantification of measurable residual disease in acute myeloid leukemia

Haematologica
Laura W DillonC S Hourigan

Abstract

Great effort is spent on developing therapies to improve the dire outcomes of those diagnosed with acute myeloid leukemia. The methods for quantifying response to therapeutic intervention have however lacked sensitivity. Patients achieving a complete remission as defined by conventional cytomorphological methods therefore remain at risk of subsequent relapse due to disease persistence. Improved risk stratification is possible based on tests designed to detect this residual leukemic burden (measurable residual disease). However, acute myeloid leukemia is a genetically diverse set of diseases, which has made it difficult to develop a single, highly reproducible, and sensitive assay for measurable residual disease. Here we present the development of a digital targeted RNA-sequencing-based approach designed to overcome these limitations by detecting all newly approved European LeukemiaNet molecular targets for measurable residual disease in acute myeloid leukemia in a single standardized assay. Iterative modifications and novel bioinformatics approaches resulted in a greater than 100-fold increase in performance compared with commercially available targeted RNA-sequencing approaches and a limit of detection as low as one leukemic c...Continue Reading

Citations

Jun 13, 2019·International Journal of Molecular Sciences·Ricardo SánchezJoaquín Martínez-López
Dec 6, 2019·British Journal of Haematology·Jack GhannamChristopher S Hourigan
Dec 21, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christopher S HouriganMitchell E Horwitz
May 28, 2020·Frontiers in Cell and Developmental Biology·Jennifer M YoestEric J Duncavage
Dec 7, 2019·Hematology·Sylvie D Freeman, Christopher S Hourigan

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Methods Mentioned

BETA
PCR
Illumina sequencing
RNA-Seq

Software Mentioned

Archer Analysis
GraphPad
Prism

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