Acute myeloid leukemia with an MN1-ETV6 fusion in a young child with Down syndrome

Cold Spring Harb Mol Case Stud. 2022 Apr 28;8(3):a006167. doi: 10.1101/mcs.a006167. Print 2022 Apr.

Abstract

Myeloid leukemia of Down syndrome (ML-DS) in young children is associated with distinct clinical and biological features and is typically initiated with oncogenic mutations in the X-linked megakaryocytic transcription factor GATA1. Here we present a 3-yr-old child with DS diagnosed with acute myeloid leukemia (AML), which lacks typical immunophenotypic and molecular characteristics of ML-DS, including GATA1 mutations. The leukemic blasts were found to have an MN1-ETV6 gene fusion, a high-risk oncofusion not previously described in DS patients. This report highlights the importance of immunophenotypic, cytogenetic, and molecular characterization of ML-DS for identification of rare cases with unique features that may benefit from treatment protocols that are more intensive than those developed for patients with typical GATA1 mutant ML-DS.

Trial registration: ClinicalTrials.gov NCT01775072.

Keywords: acute myeloid leukemia; leukemia.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Child, Preschool
  • Down Syndrome* / complications
  • Down Syndrome* / genetics
  • ETS Translocation Variant 6 Protein
  • Gene Fusion
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Proto-Oncogene Proteins c-ets / genetics*
  • Repressor Proteins / genetics*
  • Trans-Activators / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • MN1 protein, human
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Trans-Activators
  • Tumor Suppressor Proteins

Associated data

  • ClinicalTrials.gov/NCT01775072