Isolation and characterization of candidate myeloid tumor-suppressor genes on the long arm of chromosome7.

7号单体染色体是一种常见的非随机染色体异常，常见于骨髓增生异常综合征（MDS）和相关的急性髓系白血病（AML）。从7 q21带的一个共同的微缺失簇位点分离出一个以前未表征的基因，三木，泰坦Kasumi。轻度蛋白定位于高尔基体、中心体和有丝分裂纺锤体。Mild的下调扰乱了中心体的成熟和定位，导致无组织的纺锤体。细胞经历后期前停滞并在没有染色体分离的情况下退出有丝分裂或通过细胞死亡终止有丝分裂。此外，在后代中发现染色体不稳定性。Mild与纺锤体的结合取决于端锚聚合酶-1的聚（ADP-核糖）聚合酶活性。缺乏钛的老鼠看起来很正常。然而，AML通过逆转录病毒感染以非常高的频率发展，并且现在从这些小鼠中建立了共同的整合位点。这些发现表明，这三个基因是长期寻找的MDS和AML中-7/7q-的责任基因的有希望的候选者。

Monosomy 7 is a common nonrandom chromosomal abnormality found frequently in myelodysplastic syndrome (MDS) and related acute myeloid leukemia (AML). A previously uncharacterized genes, Miki, Titan Kasumi, were isolated from the site of a common microdeletion cluster in the 7q21 band. Mild protein localizes to the Golgi apparatus, centrosomes and mitotic spindles. Downregulation of Mild disturbs the maturation and positioning of centrosomes, resulting in unorganized spindles. Cells undergo pre-anaphase arrest and exit mitosis in the absence of chromosome segregation or terminate mitosis by cell death. In addition, chromosome instability is found in the progeny. The binding of Mild to spindles depends on the poly (ADP-ribose) polymerase activity of tankyrase-1. Titan-deficient mice looked normal. However, AML developed at very high frequency by infection of retrovirus and common integration sites were now establishing from these mice. These findings suggests that the three genes are promising candidates for long-sought responsible genes for -7/7q- in MDS and AML.