CBFA2T3-GLIS2-positive acute myeloid leukaemia. A peculiar paediatric entity

Br J Haematol. 2019 Feb;184(3):337-347. doi: 10.1111/bjh.15725. Epub 2018 Dec 28.


The scenario of paediatric acute myeloid leukaemia (AML), particularly non-Down syndrome acute megakaryoblastic leukaemia (non-DS-AMKL), has been recently revolutionized by the advent of large-scale, genomic sequencing technologies. In this changing landscape, a significantly relevant discovery has been represented by the identification of the CBFA2T3-GLIS2 fusion gene, which is the result of a cryptic inversion of chromosome 16. It is the most frequent chimeric oncogene identified to date in non-DS-AMKL, although it seems not to be exclusively restricted to the French-American-British M7 subgroup. The CBFA2T3-GLIS2 fusion gene characterizes a subtype of leukaemia that is specific to paediatrics, having never been identified in adults. It characterizes an extremely aggressive leukaemia, as the presence of this fusion is associated with a grim outcome in almost all of the case series reported, with overall survival rates ranging between 15% and 30%. Although the molecular basis that underlies this leukaemia subtype is still far from being completely elucidated, unique functional properties induced by CBFA2T3-GLIS2 in the leukaemogenesis driving process have been recently identified. We here review the peculiarities of CBFA2T3-GLIS2-positive AML, describing its intriguing clinical and biological behaviour and providing some challenging targeting opportunities.

Keywords: CBFA2T3-GLIS2; acute megakaryoblastic leukaemia; acute myeloid leukaemia; childhood leukaemia; leukaemia diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Animals
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 16* / genetics
  • Chromosomes, Human, Pair 16* / metabolism
  • Disease-Free Survival
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Kruppel-Like Transcription Factors* / genetics
  • Kruppel-Like Transcription Factors* / metabolism
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / mortality
  • Leukemia, Myeloid, Acute* / therapy
  • Male
  • Oncogene Proteins, Fusion* / genetics
  • Oncogene Proteins, Fusion* / metabolism
  • Repressor Proteins* / genetics
  • Repressor Proteins* / metabolism
  • Survival Rate
  • Tumor Suppressor Proteins* / genetics
  • Tumor Suppressor Proteins* / metabolism


  • CBFA2T3 protein, human
  • GLIS2 protein, human
  • Kruppel-Like Transcription Factors
  • Oncogene Proteins, Fusion
  • Repressor Proteins
  • Tumor Suppressor Proteins