Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations.
Cloning of cDNAs of the MLL gene that detect DNA rearrangements and altered RNA transcripts in human leukemic cells with 11q23 translocations.
复制标题
克隆 MLL 基因的 cDNA，用于检测具有 11q23 易位的人类白血病细胞中的 DNA 重排和 RNA 转录本的改变。
DOI：
10.1073/pnas.89.24.11794
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发表时间：
1992
影响因子：
11.1
通讯作者：
Diaz,MO
中科院分区：
文献类型：
--
作者：
McCabe,NR;Burnett,RC;Gill,HJ;Thirman,MJ;Mbangkollo,D;Kipiniak,M;vanMelle,E;Ziemin-vanderPoel,S;Rowley,JD;Diaz,MO
涉及11号染色体q23带易位的复发性染色体异常与人类髓性和淋巴性白血病以及淋巴瘤有关。我们已经确定了位于该断裂点的基因，并将其命名为MLL（髓样淋巴细胞白血病或混合系白血病）。t（4;11）、t（6;11）、t（9;11）和t（11;19）是涉及该染色体带的白血病细胞中最常见的相互易位。我们现在有证据表明，在所有这些易位的断点是在MLL基因的9-磷酸酶（kb）BamHI基因组区域内聚集。通过Southern印迹杂交，使用一个0.7 kb的BamHI的MLL基因的cDNA片段，称为MLL 0.7B，我们已经检测到的DNA重排的细胞系和患者材料与11 q23易位在这个地区。北方印迹分析表明，该基因有多个转录本，其中一些似乎是谱系特异性的。在正常前B细胞中，检测到12.5、12.0、11.5和2.0 kb的四种转录物。这些转录本也存在于单核细胞样细胞系中，并与5.0 kb转录本杂交，表明不同大小的MLL转录本的表达可能与正常的造血谱系发育有关。在具有t（4;11）的细胞系中，12.5-、12.0-和11.5-kb转录物的表达减少，并且有证据表明另外三种11.5、11.25和11.0 kb的改变的转录物。因此，这些11 q23易位导致MLL基因的重排，并可能导致MLL和易位中涉及的其他基因的功能改变。
Recurring chromosomal abnormalities involving translocations at chromosome 11 band q23 are associated with human myeloid and lymphoid leukemia as well as lymphoma. We have identified the gene located at this break-point and have named it MLL (for myeloid-lymphoid, or mixed-lineage, leukemia). The t(4;11), t(6;11), t(9;11), and t(11;19) are among the most common reciprocal translocations in leukemia cells involving this chromosomal band. We now have evidence that the breakpoints in all of these translocations are clustered within a 9-kilobase (kb) BamHI genomic region of the MLL gene. By Southern blot hybridization using a 0.7-kb BamHI cDNA fragment of the MLL gene called MLL 0.7B, we have detected rearrangements of DNA from cell lines and patient material with an 11q23 translocation in this region. Northern blot analyses indicate that this gene has multiple transcripts, some of which appear to be lineage-specific. In normal pre-B cells, four transcripts of 12.5, 12.0, 11.5, and 2.0 kb are detected. These transcripts are also present in monocytoid cell lines with additional hybridization to a 5.0-kb transcript, indicating that expression of different-sized MLL transcripts may be associated with normal hematopoietic lineage development. In a cell line with a t(4;11), the expression of the 12.5-, 12.0-, and 11.5-kb transcripts is reduced, and there is evidence of three other altered transcripts of 11.5, 11.25, and 11.0 kb. Thus, these 11q23 translocations result in rearrangements of the MLL gene and may lead to altered function(s) of MLL and of other gene(s) involved in the translocation.