Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia

Blood. 2012 Mar 15;119(11):2608-11. doi: 10.1182/blood-2010-12-324806. Epub 2012 Jan 31.


Trib1 has been identified as a myeloid oncogene in a murine leukemia model. Here we identified a TRIB1 somatic mutation in a human case of Down syndrome-related acute megakaryocytic leukemia. The mutation was observed at well-conserved arginine 107 residue in the pseudokinase domain. This R107L mutation remained in leukocytes of the remission stage in which GATA1 mutation disappeared, suggesting the TRIB1 mutation is an earlier genetic event in leukemogenesis. The bone marrow transfer experiment showed that acute myeloid leukemia development was accelerated by transducing murine bone marrow cells with the R107L mutant in which enhancement of ERK phosphorylation and C/EBPα degradation by Trib1 expression was even greater than in those expressing wild-type. These results suggest that TRIB1 may be a novel important oncogene for Down syndrome-related acute megakaryocytic leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation
  • Down Syndrome / complications
  • Down Syndrome / genetics*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Leukemia, Megakaryoblastic, Acute / etiology*
  • Leukemia, Megakaryoblastic, Acute / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mutation / genetics*
  • Oncogenes / genetics*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction


  • CCAAT-Enhancer-Binding Protein-alpha
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • TRIB1 protein, human
  • Protein Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases