Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Biol Chem. 2011 Aug;392(8-9):713-24. doi: 10.1515/BC.2011.072. Epub 2011 Jun 30.
The mixed lineage leukemia (MLL) locus is involved in more than 60 different rearrangements with a remarkably diverse group of fusion partners in approximately 10% of human leukemias. MLL rearrangements include chromosomal translocations, gene internal duplications, chromosome 11q deletions or inversions and MLL gene insertions into other chromosomes, or vice versa. MLL fusion partners can be classified into four distinct categories: nuclear proteins, cytoplasmatic proteins, histone acetyltransferases and septins. Five different septin genes (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been identified as MLL fusion partners, giving rise to chimeric fusion proteins in which the N terminus of MLL is fused, in frame, to almost the entire open reading frame of the septin partner gene. The rearranged alleles result from heterogeneous breaks in distinct introns of both MLL and its septin fusion partner, originating distinct gene fusion variants. MLL-SEPTIN rearrangements have been repeatedly identified in de novo and therapy related myeloid neoplasia in both children and adults, and some clinicopathogenetic associations are being uncovered. The fundamental roles of septins in cytokinesis, membrane remodeling and compartmentalization can provide some clues on how abnormalities in the septin cytoskeleton and MLL deregulation could be involved in the pathogenesis of hematological malignancies.
混合谱系白血病（MLL）基因座参与了超过 60 种不同的重排，与大约 10%的人类白血病中具有显著不同的融合伙伴。MLL 重排包括染色体易位、基因内重复、11q 染色体缺失或倒位以及 MLL 基因插入其他染色体，反之亦然。MLL 融合伙伴可分为四类：核蛋白、细胞质蛋白、组蛋白乙酰转移酶和 septin。已经鉴定出五个不同的 septin 基因（SEPT2、SEPT5、SEPT6、SEPT9 和 SEPT11）作为 MLL 融合伙伴，导致嵌合融合蛋白，其中 MLL 的 N 末端与 septin 伙伴基因的完整开放阅读框融合，形成框架。重排等位基因是由于 MLL 和其 septin 融合伙伴的不同内含子中的不均一断裂引起的，产生不同的基因融合变体。MLL-SEPTIN 重排在儿童和成人的新发和治疗相关髓系肿瘤中反复被发现，并且正在揭示一些临床病理关联。septin 在胞质分裂、膜重塑和区室化中的基本作用为 septin 细胞骨架异常和 MLL 失调如何参与血液恶性肿瘤的发病机制提供了一些线索。
