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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Clinical and genomic characterization of patients diagnosed with the provisional entity Acute myeloid leukemia with BCR-ABL1, a Swedish population-based study

Author

  • Christina Orsmark-Pietras
  • Niklas Landberg
  • Fryderyk Lorenz
  • Bertil Uggla
  • Martin Höglund
  • Sören Lehmann
  • Åsa Derolf
  • Stefan Deneberg
  • Petar Antunovic
  • Jörg Cammenga
  • Lars Möllgård
  • Lovisa Wennström
  • Henrik Lilljebjörn
  • Marianne Rissler
  • Thoas Fioretos
  • Vladimir Lj Lazarevic
Show all

Summary, in English

Acute myeloid leukemia (AML) with t(9;22)(q34;q11), also known as AML with BCR-ABL1, is a rare, provisional entity in the WHO 2016 classification and is considered a high-risk disease according to the European LeukemiaNet 2017 risk stratification. We here present a retrospective, population-based study of this disease entity from the Swedish Acute Leukemia Registry. By strict clinical inclusion criteria we aimed to identify genetic markers further distinguishing AML with t(9;22) as a separate entity. Twenty-five patients were identified and next-generation sequencing using a 54-gene panel was performed in 21 cases. Interestingly, no mutations were found in NPM1, FLT3 or DNMT3A, three frequently mutated genes in AML. Instead, RUNX1 was the most commonly mutated gene, with aberrations present in 38% of the cases compared to around 10% in de novo AML. Additional mutations were identified in genes involved in RNA splicing (SRSF2, SF3B1) and chromatin regulation (ASXL1, STAG2, BCOR, BCORL1). Less frequently, mutations were found in IDH2, NRAS, TET2 and TP53. The mutational landscape exhibited a similar pattern as recently described in patients with chronic myeloid leukemia (CML) in myeloid blast crisis (BC). Despite the concomitant presence of BCR-ABL1 and RUNX mutations in our cohort, both features of high-risk AML, the RUNX-mutated cases showed a superior overall survival compared to RUNX1 wildtype cases. Our results suggest that the molecular characteristics of AML with t(9;22)/BCR-ABL1 and CML in myeloid BC are similar and do not support a distinction of the two disease entities based on their underlying molecular alterations. This article is protected by copyright. All rights reserved.

Department/s

  • LUCC: Lund University Cancer Centre
  • Translational Genomic and Functional Studies of Leukemia
  • Division of Clinical Genetics

Publishing year

2021-06-01

Language

English

Pages

426-433

Publication/Series

Genes, Chromosomes and Cancer

Volume

60

Issue

6

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Medical Genetics
  • Hematology
  • Cancer and Oncology

Status

Published

Research group

  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 1045-2257