MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.
MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.
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发表时间：
1993-11
期刊：
影响因子：
8
通讯作者：
S. Iida;M. Seto;Kazuhiko Yamamoto;Hirokazu Komatsu;Arinobu Tojo;Shigetaka Asano;Nanao Kamada;Y. Ariyoshi;Toshitada Takahashi;Ryuzo Ueda
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作者：
S. Iida;M. Seto;Kazuhiko Yamamoto;Hirokazu Komatsu;Arinobu Tojo;Shigetaka Asano;Nanao Kamada;Y. Ariyoshi;Toshitada Takahashi;Ryuzo Ueda
最近，11q23的MLL基因被发现与具有11q23异常的一组白血病有关。在本研究中，我们从一个具有t(9；11)(p22；q23)易位的IMS-M1细胞系的cDNA文库中分离出MLL和一个被命名为9p22的MLLT3基因之间的嵌合cDNAs，t(9；11)(p22；q23)易位是急性单核细胞白血病中常见的一种典型核型异常。我们还分离了一个正常的MLLT3基因，发现了一个至少编码318个氨基酸的开放阅读框，其丝氨酸/脯氨酸含量较高(24.8%)。在t(11；19)和t(4；11)白血病中发现嵌合的mRNAs与MLL在框架内融合。预测的MLLT3蛋白与t(11；19)白血病涉及的19p13处的MLLT1基因有显著同源性。C末端86个氨基酸的同源性最高，达74.1%，提示该区域在t(9；11)白血病的发生中具有特殊的重要性。用MLLT3c DNA探针对正常组织进行Northern印迹分析，发现在淋巴器官中有多个转录本。一项对造血细胞系的调查显示，巨核细胞和红系细胞的信号相对较强。与先前在t(11；19)白血病中发现的一样，逆转录聚合酶链式反应(RT-PCR)可在t(9；11)白血病标本中检测到异质性MLL-MLLT3嵌合mRNAs。
Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic abnormality seen in acute monocytic leukemia. We also isolated a normal MLLT3 cDNA and found an open reading frame encoding at least 318 amino acids with high serine/proline content (24.8%). The chimeric mRNAs were demonstrated to be fused to MLL in frame, as found in t(11;19) and t(4;11) leukemias. The predicted MLLT3 protein demonstrated a significant homology to that of the MLLT1 gene at 19p13 involved in t(11;19) leukemia. The highest homology, up to 74.1%, was found in 86 amino acids of the C-terminus, suggesting that this region is of particular importance for leukemogenesis in t(9;11) leukemia. Northern blot analysis with the MLLT3 cDNA probe against normal tissues revealed multiple transcripts in lymphoid organs. A survey of hematopoietic cell lines demonstrated relatively stronger signals in cells belonging to megakaryocytic and erythroid lineages. As previously found in t(11;19) leukemia, heterogeneous MLL-MLLT3 chimeric mRNAs could be detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) in t(9;11) leukemia samples.