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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
Author(s) -
OrsmarkPietras Christina,
Landberg Niklas,
Lorenz Fryderyk,
Uggla Bertil,
Höglund Martin,
Lehmann Sören,
Derolf Åsa,
Deneberg Stefan,
Antunovic Petar,
Cammenga Jörg,
Möllgård Lars,
Wennström Lovisa,
Lilljebjörn Henrik,
Rissler Marianne,
Fioretos Thoas,
Lazarevic Vladimir Lj
Publication year - 2021
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22936
Subject(s) - myeloid leukemia , npm1 , medicine , neuroblastoma ras viral oncogene homolog , runx1 , oncology , myeloid , population , leukemia , cancer research , gene mutation , mutation , gene , genetics , biology , karyotype , cancer , chromosome , colorectal cancer , environmental health , transcription factor , kras
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 1 mutations in our cohort, both features of high‐risk AML, the RUNX1 ‐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.