Molecular mechanisms that produce secondary MDS/AML by RUNX1/AML1 point mutations

J Cell Biochem. 2011 Feb;112(2):425-32. doi: 10.1002/jcb.22974.


RUNX1/AML1 point mutations have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients. A heterozygous germline mutation of the RUNX1 gene causes a familial platelet disorder with a predisposition to AML. RUNX1 mutations have also been detected with high frequency in minimally differentiated AML M0 subtypes and myelodysplastic/myeloproliferative neoplasms. Here we propose a new disease category of myelodysplastic neoplasms (MDN) consisting of MDS refractory anemia with excess blasts and AML with myelodysplasia-related changes, including therapy-related cases. RUNX1 mutations have been detected in about 20% of patients with "MDN". Among the MDN cases, histories of radiation exposure, therapy-related myeloid neoplasms after successful treatment for acute promyelocytic leukemia, and leukemic transformation of myeloproliferative neoplasms have been reported to have a strong association with RUNX1 mutations. The mutations occur in a normal, a receptive, or a disease-committed hematopoietic stem cell. It is suspected that the "MDN" phenotypes are defined by the RUNX1 mutations in addition to some other abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Core Binding Factor Alpha 2 Subunit / genetics*
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism*
  • Models, Biological
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / metabolism*
  • Point Mutation / genetics*


  • Core Binding Factor Alpha 2 Subunit