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

Orsmark-Pietras, Christina LU ; Landberg, Niklas LU orcid ; Lorenz, Fryderyk ; Uggla, Bertil ; Höglund, Martin ; Lehmann, Sören ; Derolf, Åsa ; Deneberg, Stefan ; Antunovic, Petar and Cammenga, Jörg LU , et al. (2021) In Genes, Chromosomes and Cancer 60(6). p.426-433
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
60
issue
6
pages
8 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:33433047
  • scopus:85099965164
ISSN
1045-2257
DOI
10.1002/gcc.22936
language
English
LU publication?
yes
additional info
This article is protected by copyright. All rights reserved.
id
ce92906e-28cc-4057-a266-6079bf68b38b
date added to LUP
2021-01-17 07:56:25
date last changed
2024-12-13 01:46:33
@article{ce92906e-28cc-4057-a266-6079bf68b38b,
  abstract     = {{<p>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.</p>}},
  author       = {{Orsmark-Pietras, Christina and Landberg, Niklas and Lorenz, Fryderyk and Uggla, Bertil and Höglund, Martin and Lehmann, Sören and Derolf, Åsa and Deneberg, Stefan and Antunovic, Petar and Cammenga, Jörg and Möllgård, Lars and Wennström, Lovisa and Lilljebjörn, Henrik and Rissler, Marianne and Fioretos, Thoas and Lazarevic, Vladimir Lj}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{426--433}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes, Chromosomes and Cancer}},
  title        = {{Clinical and genomic characterization of patients diagnosed with the provisional entity Acute myeloid leukemia with BCR-ABL1, a Swedish population-based study}},
  url          = {{http://dx.doi.org/10.1002/gcc.22936}},
  doi          = {{10.1002/gcc.22936}},
  volume       = {{60}},
  year         = {{2021}},
}