Affordable Access

deepdyve-link
Publisher Website

Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing.

Authors
  • Arindrarto, Wibowo1, 2
  • Borràs, Daniel M3, 4
  • de Groen, Ruben A L5
  • van den Berg, Redmar R2
  • Locher, Irene J5
  • van Diessen, Saskia A M E5
  • van der Holst, Rosalie5
  • van der Meijden, Edith D5
  • Honders, M Willy5
  • de Leeuw, Rick H6
  • Verlaat, Wina5
  • Jedema, Inge5
  • Kroes, Wilma G M7
  • Knijnenburg, Jeroen7
  • van Wezel, Tom8
  • Vermaat, Joost S P5
  • Valk, Peter J M9
  • Janssen, Bart3
  • de Knijff, Peter6
  • van Bergen, Cornelis A M5
  • And 6 more
  • 1 Center for Computational Biology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 2 Department of Human Genetics, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 3 GenomeScan B.V, 2333 BZ, Leiden, The Netherlands. , (Netherlands)
  • 4 Department of Chemical Cell Biology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 5 Department of Hematology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 6 Forensic Laboratory for DNA Research, Department of Human Genetics, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 7 Department of Clinical Genetics, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 8 Department of Pathology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 9 Department of Hematology, Erasmus University Medical Center, 3015CN, Rotterdam, The Netherlands. , (Netherlands)
  • 10 The Delft Bioinformatics Lab, Delft University of Technology, 2628CD, Delft, The Netherlands. , (Netherlands)
  • 11 Section of Molecular Epidemiology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. , (Netherlands)
  • 12 The Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands. , (Netherlands)
  • 13 Department of Hematology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands. [email protected] , (Netherlands)
Type
Published Article
Journal
Leukemia
Publisher
Springer Nature
Publication Date
Jan 01, 2021
Volume
35
Issue
1
Pages
47–61
Identifiers
DOI: 10.1038/s41375-020-0762-8
PMID: 32127641
Source
Medline
Language
English
License
Unknown

Abstract

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics. We developed HAMLET (Human AML Expedited Transcriptomics) as bioinformatics pipeline for simultaneous detection of fusion genes, small variants, tandem duplications, and gene expression with all information assembled in an annotated, user-friendly output file. Whole transcriptome RNA sequencing was performed on 100 AML cases and HAMLET results were validated by reference assays and targeted resequencing. The data showed that HAMLET accurately detected all fusion genes and overexpression of EVI1 irrespective of 3q26 aberrations. In addition, small variants in 13 genes that are often mutated in AML were called with 99.2% sensitivity and 100% specificity, and tandem duplications in FLT3 and KMT2A were detected by a novel algorithm based on soft-clipped reads with 100% sensitivity and 97.1% specificity. In conclusion, HAMLET has the potential to provide accurate comprehensive diagnostic information relevant for AML classification, risk assessment and targeted therapy on a single technology platform.

Report this publication

Statistics

Seen <100 times