Expression and mutation analysis of genes that encode the Myc antagonists Mad1, Mxi1 and Rox in acute leukaemia
Expression and mutation analysis of genes that encode the Myc antagonists Mad1, Mxi1 and Rox in acute leukaemia
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DOI：
10.1080/10428190701342018
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Ohno, Ruzo
中科院分区：
文献类型：
--
作者：
Guo, Xiao-Ling;Pan, Ling;Ohno, Ruzo
Myc拮抗剂Mad1， Mxi1和Rox蛋白共享两个高度保守的结构域，Sin3-相互作用结构域（SID）和基本螺旋-环-螺旋亮氨酸拉链结构域（bHLHzip），这是这些蛋白在从增殖到分化的分子转换过程中发挥作用所必需的。为了鉴定人类血液恶性肿瘤中Mad1、Mxi1和Rox基因的突变，我们筛选了来自26例血液恶性肿瘤患者的10种造血细胞系、骨髓单核细胞（BMMNC）和来自30名健康志愿者的外周血单核细胞（PBMNC），采用逆转录-聚合酶链反应、单链构象多态性分析和测序。所有样品均表达Mad1、Mxi1和Rox基因。在BMMNC和PBMNC细胞系中发现了4个多态性：Mad1 2个，Mxi1 1个，Rox 1个。在患者中检测到9个错义突变：2个在Mad1中，4个在Mxi1中（3个在患者中，1个在KG-1细胞系中），3个在Rox中。健康志愿者的PBMNC未检测到突变。6例急性淋巴细胞白血病患者中，2例Mxi1突变，2例Rox突变。这些突变与较差的临床结果相关。这是首次报道Mad1， Mxi1和Rox基因在血液恶性肿瘤中表达和显示突变。
The Myc antagonists Mad1, Mxi1 and Rox proteins share two highly conserved domains, Sin3- interacting domain (SID) and basic helix- loop- helix leucine zipper domain (bHLHzip), which are essential for these proteins to function during molecular switching from proliferation to differentiation. In an attempt to identify mutations in Mad1, Mxi1 and Rox genes in human haematological malignancies, we screened 10 haematopoietic cell lines, bone marrow mononuclear cells (BMMNC) from 26 patients with haematological malignancies and peripheral blood mononuclear cells (PBMNC) from 30 healthy volunteers, using reverse transcription- polymerase chain reaction, single strand conformation polymorphism analysis and sequencing. Mad1, Mxi1 and Rox genes were expressed in all samples. Four polymorphisms were found in cell lines BMMNC and PBMNC: two in Mad1, one in Mxi1 and one in Rox. Nine missense mutations were detected: two in Mad1 in patients, four in Mxi1 (three in patients and one in KG-1 cell line), and three in Rox in patients. No mutations were detected in PBMNC from healthy volunteers. Among six patients with acute lymphoblastic leukaemia, two had Mxi1 mutations and another two had Rox mutations. These mutations were associated with poorer clinical outcomes. This is the first report to show that Mad1, Mxi1 and Rox genes were expressed and displayed mutations in haematological malignancies.