急性白血病中因MLL 5'端重复部分插入10p12导致的隐匿性MLL-AF10融合：一例报告

Cryptic MLL-AF10 fusion caused by insertion of duplicated 5' part of MLL into 10p12 in acute leukemia: a case report.

作者信息

Jarosova Marie, Takacova Sylvia, Holzerova Milena, Priwitzerova Monika, Divoka Martina, Lakoma Ilona, Mihal Vladimir, Indrak Karel, Divoky Vladimir

机构信息

Department of Hemato-oncology, Palacky University Hospital, Olomouc, Czech Republic.

出版信息

Cancer Genet Cytogenet. 2005 Oct 15;162(2):179-82. doi: 10.1016/j.cancergencyto.2005.03.012.

DOI:10.1016/j.cancergencyto.2005.03.012

PMID:16213369

Abstract

Chromosomal translocations involving the mixed lineage leukemia gene (MLL) located at 11q23 belong to common chromosomal abnormalities in both acute lymphoblastic (ALL) and acute myeloid leukemias (AML). It has been suggested that the mechanism of MLL leukemogenesis might be a result of a gain-of-function effect of the MLL fusion gene and simultaneous loss of function of one of the MLL alleles (haploinsufficiency). One of the recurrent translocations in AML-M5 involves chromosomal locus 10p12 and results in the MLL-AF10 fusion gene. Several mechanisms leading to MLL-AF10 fusion have been reported, and they have involved rearrangement of the 11q23 region. We present a detailed structural analysis of an AML case with an extra copy of the 5' part of MLL region and its insertion into the short arm of chromosome 10, resulting in an MLL-AF10 fusion without rearrangement of the MLL alleles on both chromosomes 11. Our observation supports a role for a simple MLL gain-of-function in leukemogenesis.

摘要

涉及位于11q23的混合谱系白血病基因（MLL）的染色体易位是急性淋巴细胞白血病（ALL）和急性髓细胞白血病（AML）中常见的染色体异常。有人提出，MLL白血病发生的机制可能是MLL融合基因功能获得效应以及MLL等位基因之一功能同时丧失（单倍体不足）的结果。AML-M5中反复出现的易位之一涉及染色体位点10p12，并导致MLL-AF10融合基因。已经报道了几种导致MLL-AF10融合的机制，它们都涉及11q23区域的重排。我们对一例AML病例进行了详细的结构分析，该病例中MLL区域5'部分有一个额外拷贝，并插入到10号染色体短臂，导致MLL-AF10融合，而两条11号染色体上的MLL等位基因均未重排。我们的观察结果支持单纯的MLL功能获得在白血病发生中的作用。