Sercan Zeynep, Pehlivan Melek, Gokturk Dilek, Sercan Hakki Ogun
Department of Medical Biology and Genetics, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.
Tumori. 2009 Nov-Dec;95(6):836-9. doi: 10.1177/030089160909500633.
Studies reporting activated Wnt signaling in all stages of chronic myeloid leukemia (CML) have demonstrated that deregulation of the pathway plays a role in the pathogenesis of this disease. Several reports have suggested mechanisms for the deregulated Wnt signaling and beta-catenin stabilization observed in CML. One possible mechanism for beta-catenin stabilization could be the acquisition of mutations at its N-terminal domain, especially in the third exon where it is marked via phosphorylation for degradation. We sought to determine whether mutations in the third exon of the beta-catenin gene are responsible for the observed Wnt activation in CML.
We screened bone marrow specimens from 33 patients with CML in the chronic phase and also examined the K562 cell line for beta-catenin mutations.
None of the patients nor the K562 cell line were found to carry mutations.
Beta-catenin amino-terminal mutations are not observed or very rare and therefore are not the underlying mechanism of activated Wnt signaling in CML.
有关慢性髓性白血病（CML）各阶段Wnt信号激活的研究表明，该信号通路失调在本病发病机制中起作用。多项报告提出了CML中Wnt信号失调及β-连环蛋白稳定化的机制。β-连环蛋白稳定化的一种可能机制可能是其N端结构域发生突变，尤其是在通过磷酸化标记进行降解的第三个外显子处。我们试图确定β-连环蛋白基因第三个外显子中的突变是否是CML中观察到的Wnt激活的原因。
我们筛选了33例慢性期CML患者的骨髓标本，并检测了K562细胞系中的β-连环蛋白突变。
未发现患者及K562细胞系携带突变。
未观察到或非常罕见β-连环蛋白氨基端突变，因此它不是CML中Wnt信号激活的潜在机制。
