MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25)
MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25)
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DOI：
10.1073/pnas.96.11.6428
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发表时间：
1999-05-25
影响因子：
11.1
通讯作者：
Zeleznik-Le, NJ
中科院分区：
文献类型：
--
作者：
Osaka, M;Rowley, JD;Zeleznik-Le, NJ
MLL（ALL1，Htrx; HRX）位于染色体11q23带，在既往接受过DNA拓扑异构酶II抑制剂治疗的治疗相关急性髓性白血病患者中经常发生重排。在这项研究中，我们已经确定了MLL的融合伙伴在一个10岁的女性谁开发治疗相关的急性髓细胞白血病治疗后17个月的霍奇金病。该患者的白血病细胞具有t（11; 17）（q23; q25），如Southern印迹分析所示，其涉及MLL。通过使用衔接子逆转录酶-PCR、5 'cDNA末端快速扩增和BLAST数据库分析的组合从白血病细胞的cDNA克隆伴侣基因以鉴定表达的序列标签。该基因全长2.8kb，是septin家族的一个新成员，因此命名为MSF（MLL septin-like fusion）。一个主要的4 kb的转录MSF无处不在的表达，1.7 kb的转录被发现在大多数组织。一个额外的3-kb的转录只在造血组织中发现。用MLL外显子5正向引物和反向引物在MSF中扩增，获得大小合适的产物。MSF与hCDCrel-1高度同源，hCDCrel-1是白血病MLL的伴侣基因，具有t（11; 22）（q23; q11.2）。MSF的进一步分析可能有助于描述MLL伴侣基因在白血病中的功能，特别是在治疗相关的白血病中。
MLL (ALL1, Htrx; HRX), which is located on chromosome band 11q23, frequently is rearranged in patients with therapy-related acute myeloid leukemia who previously were treated with DNA topoisomerase II inhibitors. In this study, we have identified a fusion partner of MLL in a 10-year-old female who developed therapy-related acute myeloid leukemia 17 months after treatment for Hodgkin's disease. Leukemia cells of this patient had a t(11;17) (q23;q25), which involved MLL as demonstrated by Southern blot analysis. The partner gene was cloned from cDNA of the leukemia cells by use of a combination of adapter reverse transcriptase-PCR, rapid amplification of 5' cDNA ends, and BLAST database analysis to identify expressed sequence tags. The full-length cDNA of 2.8 kb was found to be an additional member of the septin family, therefore it was named MSF (MLL septin-like fusion), Members of the septin family conserve the GTP binding domain, localize in the cytoplasm, and interact with cytoskeletal filaments. A major 4-kb transcript of MSF was expressed ubiquitously; a 1.7-kb transcript was found in most tissues. An additional 3-kb transcript was found only in hematopoietic tissues. By amplification with MLL exon 5 forward primer and reverse primers in MSF, the appropriately sized products were obtained. MSF is highly homologous to hCDCrel-1, which is a partner gene of MLL in leukemias with a t(11;22)(q23;q11.2). Further analysis of MSF may help to delineate the function of MLL partner genes in leukemia, particularly in therapy-related leukemia.