Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)

Cancer Gene Ther. 2020 Nov;27(10-11):810-818. doi: 10.1038/s41417-019-0159-x. Epub 2020 Jan 6.


Chromosome translocation t(12;22)(p13;q12)/MN1-ETV6 and MN1 overexpression confer a subset of adverse prognostic AML but so far lack in-depth research. We focused on the clinical course and comprehensive genetic analysis of eight cases with t(12;22)(p13;q12) and one with t(12;17;22) (p13;q21;q13) to elucidate their molecular etiology and outcomes of allogeneic hemopoietic stem cell transplantation (allo-HSCT). The total incidence of t(12;22)(p13;q12) and related translocations was 0.32% in myeloid neoplasms. These patients were confirmed to have dismal prognosis when treated only with chemotherapy, and we firstly provided evidence that they can significantly benefit from timely allo-HSCT. Five cases were MN1-ETV6 positive, and a novel MN1-STAT3 fusion was identified in the patient with triadic translocation. Significant MN1 overexpression was observed in all three MN1-fusion-negative cases. Genetic analysis highlighted the evidence of an ectopic super-enhancer associated orchestrated mechanism of MN1 overexpression and ETV6 haploinsufficiency in t(12;22)(p13;q12) myeloid neoplasms, rather than the conventional thought of MN1-ETV6 fusion formation. We also disclosed the high concomitance of trisomy 8 and 531 Kbps focal 8q duplication in t(12;22)(p13;q12) cases. The new perspective about this entity of disease will enlighten further research to define the mechanism of tumorigenesis and discover effective treatments for MN1-driven malignancies.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Genomics / methods*
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / genetics*
  • Trans-Activators / pharmacology
  • Trans-Activators / therapeutic use*
  • Transcription Factors / genetics*
  • Translocation, Genetic / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / pharmacology
  • Tumor Suppressor Proteins / therapeutic use
  • Young Adult


  • MN1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins