Molecular mechanisms that produce secondary MDS/AML by RUNX1/AML1 point mutations.
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.
Division of Radiation Information Registry, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan.
Yuka
Y
Harada
Hironori
H
Harada
D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics*
D050676:Core Binding Factor Alpha 2 Subunit