Dimerization of MLL fusion proteins immortalizes hematopoietic cells

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• 作者：Mary Ellen Martin ; Thomas A. Milne ; Sebastien Bloyer ; Karine Galoian ; Weiping Shen ; Denise Gibbs ; Hugh W. Brock ; Robert Slany ; Jay L. Hess
• 刊名：Cancer Cell
• 出版年：2003
• 出版时间：September 2003
• 年：2003
• 卷：4
• 期：3
• 页码：197-207
• 全文大小：568 K

文摘

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.