Department of Genetics, University of Erlangen, Erlangen, Germany.
Future Oncol. 2009 Oct;5(8):1271-81. doi: 10.2217/fon.09.96.
Genomic rearrangements of the locus 11q23 are frequently observed in aggressive acute leukemias with poor prognosis. These chromosomal aberrations fuse the mixed-lineage leukemia (MLL) gene to one of more than 50 partners. The resulting mixed-lineage leukemia fusions often code for chimeric transcriptional activators, which are able to transform normal hematopoietic cells through the deregulation of leukemogenic target genes. This review provides a concise overview about the known functions encoded in MLL and the respective fusion partners. Additionally, the roles of some target genes, as well as co-factors of mixed-lineage leukemia fusion proteins, are described with an emphasis on recent advances potentially uncovering novel therapeutic targets.
11q23 位点的基因组重排经常在预后不良的侵袭性急性白血病中观察到。这些染色体畸变将混合谱系白血病(MLL)基因融合到 50 多个伙伴之一。由此产生的混合谱系白血病融合物通常编码嵌合转录激活因子,通过失调白血病靶基因,能够转化正常造血细胞。这篇综述简要概述了 MLL 和相应融合伙伴所编码的已知功能。此外,还描述了一些靶基因以及混合谱系白血病融合蛋白的共同因子的作用,重点介绍了可能揭示新的治疗靶点的最新进展。