t(3;8)(q26.2;q24) Often Leads to MECOM/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and/or Disease Progression

J Mol Diagn. 2019 Mar;21(2):343-351. doi: 10.1016/j.jmoldx.2018.10.005. Epub 2018 Dec 19.

Abstract

t(3;8)(q26.2;q24) is a rare recurrent cytogenetic abnormality that is associated with myeloid neoplasms. Of 20 patients with t(3;8)(q26.2,q24), 8 had therapy-related acute myeloid leukemia (AML), 3 therapy-related myelodysplastic syndrome, 4 blast phase of chronic myeloid leukemia, 1 relapsed AML, 1 AML transformed from chronic myelomonocytic leukemia, 1 blast phase of an unclassifiable myeloproliferative neoplasm, 1 de novo myelodysplastic syndrome, and 1 de novo AML. Nineteen patients presented with cytopenia. Multilineage dysplasia was observed in 16/18 patients, and megakaryocytes were markedly decreased in 11/20 patients. Blasts showed a primitive myeloid immunophenotype in 17 patients, negative for myeloperoxidasein in 14/17, and aberrant CD7 expression in 5/17 patients. Fluorescence in situ hybridization showed MECOM rearrangement in 18/19 and MYC in 16/18 patients. Myc was shown to be expressed in all 14 cases assessed. Gene mutation testing was performed in 14 patients, and 7 showed at least one mutation including ASXL1 (2/6), TET2 (2/6), SRSF2 (2/6), and NRAS (2/13). At last clinical follow-up, 18 patients died and 2 were alive with persistent disease, with a median survival of 6 months. The authors conclude that t(3;8)(q26.2;q24) often leads to MECOM and MYC rearrangement, occurs predominantly in therapy-related myeloid neoplasms or at disease progression, and shares some similarities with myeloid neoplasms associated with inv(3)/GATA2-MECOM. Patients with myeloid neoplasms associated with t(3;8)(q26.2;q24) have a dismal outcome.

MeSH terms

  • Adult
  • Aged
  • Cytogenetics
  • Disease Progression
  • Female
  • Humans
  • Immunophenotyping
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • MDS1 and EVI1 Complex Locus Protein / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Translocation, Genetic / genetics*
  • Young Adult

Substances

  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • Proto-Oncogene Proteins c-myc