人源 MLL-AF9 过表达诱导斑马鱼造血系统异常扩张。

Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish.

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Biomed Res Int. 2018 May 30;2018:6705842. doi: 10.1155/2018/6705842. eCollection 2018.

DOI:10.1155/2018/6705842

PMID:30003105

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5998191/

Abstract

The 11q23 of the mixed lineage leukemia 1 () gene plays a crucial role in early embryonic development and hematopoiesis. The fusion gene, resulting from chromosomal translocation, often leads to acute myeloid leukemia with poor prognosis. Here, we generated a zebrafish model expressing the human fusion gene. Microinjection of human mRNA into zebrafish embryos resulted in enhanced hematopoiesis and the activation of downstream genes such as and cluster genes. Embryonic MLL-AF9 expression upregulated HSPC and myeloid lineage markers. Doxorubicin and MI-2 (a menin inhibitor) treatments significantly restored normal hematopoiesis in MLL-AF9-expressing animals. This study provides insight into the role of MLL-AF9 in zebrafish hematopoiesis and establishes a robust and efficient in vivo model for high-throughput drug screening.

摘要

混合谱系白血病 1 基因的 11q23 区域在早期胚胎发育和造血过程中发挥着关键作用。由染色体易位导致的融合基因常导致预后不良的急性髓系白血病。在此，我们构建了一个表达人融合基因的斑马鱼模型。将人 mRNA 显微注射到斑马鱼胚胎中，导致造血增强，并激活下游基因，如和簇基因。胚胎期 MLL-AF9 的表达上调了 HSPC 和髓系标记物。多柔比星和 MI-2（一种门冬酰胺酶抑制剂）处理显著恢复了表达 MLL-AF9 的动物的正常造血。本研究深入了解了 MLL-AF9 在斑马鱼造血中的作用，并建立了一个强大且高效的高通量药物筛选的体内模型。