Dimerization of MLL fusion proteins immortalizes hematopoietic cells

被引：135

作者：

Martin, ME

Milne, TA

Bloyer, S

Galoian, K

Shen, WP

Gibbs, D

Brock, HW

Slany, R

Hess, JL ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[3] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada

[4] Univ Erlangen Nurnberg, Dept Genet, D-91058 Erlangen, Germany

来源：

CANCER CELL | 2003年 / 4卷 / 03期

关键词：

D O I：

10.1016/S1535-6108(03)00214-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

MLL fusion proteins are leukemogenic, but their mechanism is unclear. Induced dimerization of a truncated MLL immortalizes bone marrow and imposes a reversible block on myeloid differentiation associated with upregulation of Hox a7, a9, and Meis1. Both dimerized MLL and exon-duplicated MLL are potent transcriptional activators, suggesting a link between dimerization and partial tandem duplication of DNA binding domains of MLL. Dimerized MLL binds with higher affinity than undimerized MLL to a CpG island within the Hox a9 locus. However, MLL-AF9 is not dimerized in vivo. The data support a model in which either MLL dimerization/exon duplication or fusion to a transcriptional activator results in Hox gene upregulation and ultimately transformation.

引用

页码：197 / 207

页数：11