生物
造血
干细胞
红细胞生成
癌症研究
HMGA2型
祖细胞
骨髓
分子生物学
非翻译区
免疫学
基因
遗传学
内科学
核糖核酸
小RNA
医学
贫血
作者
Kazuhiko Ikeda,Philip J. Mason,Monica Bessler
出处
期刊:Blood
[American Society of Hematology]
日期:2011-06-02
卷期号:117 (22): 5860-5869
被引量:96
标识
DOI:10.1182/blood-2011-02-334425
摘要
Overexpression of high mobility group AT-hook 2 (HMGA2) is found in a number of benign and malignant tumors, including the clonal PIGA(-) cells in 2 cases of paroxysmal nocturnal hemoglobinuria (PNH) and some myeloproliferative neoplasms (MPNs), and recently in hematopoietic cell clones resulting from gene therapy procedures. In nearly all these cases overexpression is because of deletions or translocations that remove the 3' untranslated region (UTR) which contains binding sites for the regulatory micro RNA let-7. We were therefore interested in the effect of HMGA2 overexpression in hematopoietic tissues in transgenic mice (ΔHmga2 mice) carrying a 3'UTR-truncated Hmga2 cDNA. ΔHmga2 mice expressed increased levels of HMGA2 protein in various tissues including hematopoietic cells and showed proliferative hematopoiesis with increased numbers in all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis and erythropoietin-independent erythroid colony formation. ΔHmga2-derived BM cells had a growth advantage over wild-type cells in competitive repopulation and serial transplantation experiments. Thus overexpression of HMGA2 leads to proliferative hematopoiesis with clonal expansion at the stem cell and progenitor levels and may account for the clonal expansion in PNH and MPNs and in gene therapy patients after vector insertion disrupts the HMGA2 locus.
科研通智能强力驱动
Strongly Powered by AbleSci AI