Division of Radiation Information Registry, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan.
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.
RUNX1/AML1 点突变已在骨髓增生异常综合征（MDS）和急性髓系白血病（AML）患者中被发现。RUNX1 基因的杂合性种系突变可导致具有 AML 易感性的家族性血小板疾病。RUNX1 突变也在低分化 AML M0 亚型和骨髓增生异常/骨髓增生性肿瘤中高频检出。在此，我们提出了一个新的骨髓增生异常肿瘤（MDN）疾病类别，包括 MDS 伴原始细胞过多性难治性贫血和伴 MDS 相关改变的 AML，包括治疗相关病例。在约 20%的“MDN”患者中检测到 RUNX1 突变。在 MDN 病例中，曾有辐射暴露史、急性早幼粒细胞白血病成功治疗后的治疗相关髓系肿瘤以及骨髓增生性肿瘤的白血病转化，与 RUNX1 突变有很强的相关性。突变发生在正常、有接受能力或疾病定型的造血干细胞中。据推测，除了其他一些异常外，“MDN”表型还由 RUNX1 突变定义。
