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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • Norrland University Hospital
  • Örebro University Hospital
  • Uppsala University Hospital
  • Sahlgrenska University Hospital
  • Karolinska University Hospital
  • Linköping University Hospital
  • Sahlgrenska University Hospital, Wallenberg Laboratory
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Hematology
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)426-433
Number of pages8
JournalGenes, Chromosomes and Cancer
Volume60
Issue number6
Early online date2021 Jan 12
Publication statusPublished - 2021 Jun 1
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

This article is protected by copyright. All rights reserved.