Liu P, Tarlé S A, Hajra A, Claxton D F, Marlton P, Freedman M, Siciliano M J, Collins F S
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Science. 1993 Aug 20;261(5124):1041-4. doi: 10.1126/science.8351518.
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 CBF beta, also known as PEBP2 beta, 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 CBF beta with the tail region of SMMHC. The repeated coiled coil of SMMHC may result in dimerization of the CBF beta fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation.
16号染色体的臂间倒位[inv(16)(p13q22)]是一种与急性髓系白血病相关的特征性核型异常，最常见于M4Eo亚型。通过酵母人工染色体和黏粒克隆确定了16p和16q的断点，并鉴定了参与这种倒位的两个基因。在16q上，倒位发生在CBFβ（也称为PEBP2β）编码区末端附近，CBFβ是一种调节T细胞中表达基因的异二聚体转录因子的一个亚基；在16p上，一个平滑肌肌球蛋白重链(SMMHC)基因(MYH11)被中断。在检测的6个inv(16)患者样本中，均证实存在一个框内融合信使核糖核酸，它将CBFβ的前165个氨基酸与SMMHC的尾部区域连接起来。SMMHC重复的卷曲螺旋可能导致CBFβ融合蛋白二聚化，这反过来会导致转录调控改变，并促进白血病转化。
