β-catenin基因在白血病患者中的表达及其临床意义

目的检测β-catenin在白血病患者中的表达，初步探讨其在白血病中的作用。方法采用半定量RT—PCR方法检测β-catenin在白血病患者中的表达，同时对部分标本应用免疫细胞化学检测其蛋白表达水平，结合临床资料分析其表达的意义。结果骨髓单个核细胞（MNC）中β-cateninmRNA在急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）患者中的表达（中位值分别为0．7593、0．6415）均明显高于正常人（0．3597）（P值分别为0．001、0．016），也明显高于慢性粒细胞白血病（CML）慢性期患者（0．2571）（P值分别为0．001、0．008），但在AML和ALL之间差异无统计学意义（P〉0．05）。β-catenin在CML慢性期患者的表达与正常人相比差异无统计学意义，但是在急变和加速期患者（0．9152）中明显增高，与急性白血病水平相当。按照FAB分型，β-catenin在AMLM，亚型中高表达，而在M3中表达明显低于其他亚型。免疫细胞化学结果显示，正常MNC β-catenin主要分布于细胞膜和细胞质，而在白血病细胞中，除M3外几乎均可以在细胞核中检测到其程度不一的表达。患者年龄、白细胞计数、高危核型以及治疗反应与β-catenin均无显著相关，但在AML组β-catenin与CD34抗原表达有明显相关性。结论经典的Wnt／β-catenin信号传导途径有可能在急性白血病及CML急变和加速期中被激活。

The expression of β-catenin and its significance in leukemia cells

OBJECTIVE: To investigate the expression of beta-catenin in patients with leukemia and explore its significance in leukemias. METHODS: RT-PCR was used to detect the expression of beta-catenin in bone marrow mononuclear cells (BMMNCs) from patients with leukemia. Immunocytochemistry was in some of patients to detect the distribution of beta-catenin at the same time. The clinical significance of beta-catenin was analyzed in combination with patients' clinical information. RESULTS: Expression of beta-catenin was statistically higher in acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) samples than in normal donors (P = 0.001 and 0.016 respectively) and chronic phase chronic myloid leukemia (CML) patients (P = 0.001 and P = 0.008 respectively), while there was no statistic difference between AML and ALL patients (P = 0.58). In addition, beta-catenin expression in chronic phase CML patients was like that in normal donors (P = 0.49), but increased significantly in blast crisis and accelerated phase. Immunocytochemical analysis revealed that BMMNCs from normal donors expressed beta-catenin on the plasma membrane and cytoplasma, while those from acute leukemia expressed beta-catenin to varying degrees in the nucleus as well. The expression of beta-catenin gene statistically showed the highest level in M5 (n = 15) and the lowest level in M3 (n = 18). No clinical features, such as, age, initial WBC count, therapy response rate, blast cell numbers or cytogenetic risk was found to be correlated with the expression of beta-catenin excepting for CD34+ positive rate (P = 0.004) in AML. CONCLUSION: As a key mediator of Wnt signal transduction way, overexpression of beta-catenin in leukemia cells indicates that it might be aberrantly activated in acute leukemia, accelerated or blastic phase of CML.