Activating mutations in human acute megakaryoblastic leukemia

Blood. 2008 Nov 15;112(10):4220-6. doi: 10.1182/blood-2008-01-136366. Epub 2008 Aug 28.


Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. To gain insight into the oncogenic process leading to acute megakaryoblastic leukemia (AMKL), we performed sequence analyses of a subset of oncogenes known to be activated in human myeloid and myeloproliferative disorders. In a series of human AMKL samples from both Down syndrome and non-Down syndrome patients, mutations were identified within KIT, FLT3, JAK2, JAK3, and MPL genes, with a higher frequency in DS than in non-DS patients. The novel mutations were analyzed using BaF3 cells, showing that JAK3 mutations were activating mutations. Finally, we report a novel constitutively active MPL mutant, MPLT487A, observed in a non-Down syndrome childhood AMKL that induces a myeloproliferative disease in mouse bone marrow transplantation assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Down Syndrome / genetics*
  • Down Syndrome / metabolism
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Megakaryoblastic, Acute / genetics*
  • Leukemia, Megakaryoblastic, Acute / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Mutation*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Transplantation


  • Neoplasm Proteins