Detection of rare reciprocal RUNX1 rearrangements by next-generation sequencing in acute myeloid leukemia

Genes Chromosomes Cancer. 2020 Apr;59(4):268-274. doi: 10.1002/gcc.22829. Epub 2019 Dec 2.


Reciprocal RUNX1 fusions are traditionally found in up to 10% of acute myeloid leukemia (AML) patients, usually associated with a translocation (8;21)(q22;q22) corresponding to the RUNX1-RUNX1T1 fusion gene. So far, alternative RUNX1 rearrangements have been reported only rarely in AML, and the few reports so far have focused on results based on cytogenetics, fluorescence in situ hybridization, and polymerase chain reaction. Acknowledging the inherent limitations of these diagnostic techniques, the true incidence of rare RUNX1 rearrangements may be underestimated. In this report, we present two cases of adult AML, in which we detected rare RUNX1 rearrangements not by conventional cytogenetics but rather by next-generation panel sequencing. These include t(16;21)(q24;q22)/RUNX1-CBFA2T3 and t(7;21)(p22;q22)/RUNX1-USP42, respectively. In both patients the AML was therapy-related and associated with additional structural and numerical alterations thereby conferring bad prognosis. This is in line with previous reports on rare RUNX1 fusions in AML and emphasizes the clinical importance of their detection. In summary, our report not only confirms the clinical utility of NGS for diagnostics of rare reciprocal rearrangements in AML in a real-life scenario but also sheds light on the variety and complexity within AML. It further emphasizes the need for collection of additional cases for deepening insights on their clinical meaning as well as their frequency.

Keywords: acute myeloid leukemia; myeloid gene panel; new minimal residual disease marker; next-generation sequencing; rare RUNX1 rearrangements.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 16
  • Chromosomes, Human, Pair 21
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Gene Rearrangement*
  • Genetic Association Studies
  • High-Throughput Nucleotide Sequencing
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Oncogene Proteins, Fusion / genetics
  • Repressor Proteins / genetics
  • Translocation, Genetic*


  • Biomarkers, Tumor
  • CBFA2T3 protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 protein, human
  • Repressor Proteins