FUSION BETWEEN TRANSCRIPTION FACTOR CBF-BETA/PEBP2-BETA AND A MYOSIN HEAVY-CHAIN IN ACUTE MYELOID-LEUKEMIA
FUSION BETWEEN TRANSCRIPTION FACTOR CBF-BETA/PEBP2-BETA AND A MYOSIN HEAVY-CHAIN IN ACUTE MYELOID-LEUKEMIA
复制标题
DOI：
10.1126/science.8351518
复制
发表时间：
1993-08-20
期刊：
影响因子：
56.9
通讯作者：
COLLINS, FS
中科院分区：
文献类型：
--
作者：
LIU, P;TARLE, SA;COLLINS, FS
16号染色体臂间倒位[inv（16）（p13 q22）]是与急性髓细胞白血病相关的特征性核型异常，最常见于M4 Eo亚型。利用酵母人工染色体和粘粒克隆技术定位了16 p和16 q的断裂点，并鉴定了参与倒位的两个基因。在16 q上，倒位发生在CBF β（也称为PEBP 2 β）编码区的末端附近，CBF β是T细胞中表达的异二聚体转录因子调节基因的亚基;在16 p上，平滑肌肌球蛋白重链（SMMHC）基因（MYH 11）被中断。在测试的六个inv（16）患者样本中的六个中，证实了将CBF β的前165个氨基酸与SMMHC的尾区连接的框内融合信使RNA。SMMHC的重复卷曲螺旋可能导致CBF β融合蛋白的二聚化，这反过来又会导致转录调控的改变，并有助于白血病转化。
The pericentric inversion of chromosome 16 [inv(16)(p13q22)] is a characteristic karyotypic abnormality associated with acute myeloid leukemia, most commonly of the M4Eo subtype. The 16p and 16q breakpoints were pinpointed by yeast artificial chromosome and cosmid cloning, and the two genes involved in this inversion were identified. On 16q the inversion occurred near the end of the coding region for CBFbeta, also known as PEBP2beta, a subunit of a heterodimeric transcription factor regulating genes expressed in T cells; on 16p a smooth muscle myosin heavy chain (SMMHC) gene (MYH11) was interrupted. In six of six inv(16) patient samples tested, an in-frame fusion messenger RNA was demonstrated that connected the first 165 amino acids of CBFbeta with the tail region of SMMHC. The repeated coiled coil of SMMHC may result in dimerization of the CBFbeta fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation.