Slape Christopher, Lin Ying Wei, Hartung Helge, Zhang Zhenhua, Wolff Linda, Aplan Peter D
Genetics Branch, Center for CAncer Research, NCI, NIH, Bethesda, MD 20889-5105, USA.
J Natl Cancer Inst Monogr. 2008(39):64-8. doi: 10.1093/jncimonographs/lgn014.
The myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplasia, and a propensity for transformation to acute myeloid leukemia (AML). A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene, most commonly leading to fusions of NUP98 with abd-b group HOX genes, including HOXD13. We used vav regulatory elements to direct expression of a NUP98-HOXD13 (NHD13) fusion gene in hematopoietic tissues. NHD13 transgenic mice faithfully recapitulate all the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia and apoptosis, and transformation to acute leukemia. The MDS that develops in NHD13 transgenic mice is highly lethal; within 14 months, 90% of the mice died of either leukemic transformation or severe anemia and leukopenia due to progressive MDS. These mice provide a preclinical model that can be used for the evaluation of MDS therapy and biology.
骨髓增生异常综合征（MDS）是一组克隆性造血干细胞疾病，其特征为造血无效、外周血细胞减少、发育异常以及有转化为急性髓系白血病（AML）的倾向。多种遗传畸变与MDS相关，包括涉及NUP98基因的染色体易位，最常见的是导致NUP98与abd - b组HOX基因融合，包括HOXD13。我们利用vav调控元件在造血组织中指导NUP98 - HOXD13（NHD13）融合基因的表达。NHD13转基因小鼠忠实地重现了MDS的所有关键特征，包括外周血细胞减少、骨髓发育异常和凋亡，以及转化为急性白血病。NHD13转基因小鼠中发生的MDS具有高度致死性；在14个月内，90%的小鼠死于白血病转化或由于进行性MDS导致的严重贫血和白细胞减少。这些小鼠提供了一个可用于评估MDS治疗和生物学特性的临床前模型。
