AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms

Blood. 2009 Dec 10;114(25):5201-5. doi: 10.1182/blood-2009-06-223982.


Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages. Some patients exhibit leukemic transformation (LT) by unknown mechanisms, and chemotherapy may increase the risk of LT. To clarify the molecular mechanisms of LT, gene alterations involved in LT from patients in the chronic phase (CP) of MPNs were identified. Among 18 patients who progressed to leukemia, AML1/RUNX1 mutations were detected in 5 patients at the LT but in none at the CP. To investigate the leukemogenic effect of AML1/RUNX1 mutants, the AML1D171N mutant was transduced into CD34(+) cells from patients in the CP of MPNs. The D171N transduction resulted in proliferation of immature myeloid cells, enhanced self-renewal capacity, and proliferation of primitive progenitors. Taken together, these results indicate that AML1/RUNX1 point mutations may have a leukemogenic potential in MPN stem cells, and they may promote leukemic transformation in MPN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / metabolism
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cells, Cultured
  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism
  • Female
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunoblotting
  • Leukemia / genetics
  • Leukemia / pathology*
  • Male
  • Middle Aged
  • Myeloproliferative Disorders / genetics
  • Myeloproliferative Disorders / pathology*
  • Point Mutation*
  • Retroviridae / genetics
  • Transfection


  • Antigens, CD34
  • Core Binding Factor Alpha 2 Subunit
  • RUNX1 protein, human
  • Green Fluorescent Proteins