锌指蛋白ZFX在儿童B系急性淋巴细胞性白血病中的表达及意义

Expression of zinc finger protein X-linked in childhood B lineage acute lymphoblastic leukemia

摘要:

目的：研究儿童B系急性淋巴细胞性白血病（B-ALL）患者骨髓单个核细胞中X染色体耦联锌指蛋白（ZFX）的表达及其与白血病预后的关系。方法：通过Western blot方法检测白血病细胞株（REH、HL-60、NB4、K562）中ZFX蛋白的表达；利用PCR方法扩增获得全长ZFX，并测序验证；通过实时定量PCR检测82例初发B-ALL儿童骨髓样本，24例B-ALL缓解期样本，以及64例骨折或先天性心脏病手术患儿样本(对照组)ZFX的表达；并根据治疗3年内有无骨髓或中枢神经系统复发分为预后好组和预后差组，比较两组患儿初发时骨髓中ZFX mRNA的表达水平。结果：ZFX蛋白在白血病细胞株REH、HL-60、NB4和K562中均有表达。初发ALL组骨髓中ZFX mRNA表达高于对照组（P＜0.01）；ALL缓解组ZFX mRNA表达明显低于ALL初发组（P<0.01）；预后差的ALL患儿初发骨髓中ZFX mRNA的表达高于预后好的患儿（P＜0.05）。结论ZFX在儿童B-ALL中高表达，且预后差组表达相对较高，提示它可能在B-ALL预后判断中有重要意义。

Abstract:

OBJECTIVE: To study the expression of zinc finger protein X-linked (ZFX) in bone marrow mononuclear cells (BMMCs) of children with B lineage acute lymphoblastic leukemia (B-ALL) and its relationship with prognosis. METHODS: The expression of ZFX in human leukemia cell lines (REH, HL-60, NB4 and K562) was measured by Western blot. ZFX gene was cloned by PCR from one patient and DNA sequencing technology was used to confirm it. Real-time PCR was used for detecting ZFX mRNA expression in the BMMCs of 82 children with newly-diagnosed B-ALL, 24 children with complete remission (CR) after induction therapy and 64 control children (fracture or congenital heart disease patients). According to the presence of bone marrow or central nervous system relapse during a follow-up of 3 years, the patients were identified as having a good or poor prognosis. Their ZFX mRNA levels in BMMCs at diagnosis were compared. RESULTS: ZFX protein was expressed in human leukemia cell lines REH, HL-60, NB4 and K562. ZFX mRNA expression was significantly higher in the newly-diagnosed ALL group than in the control group (P＜0.01). ZFX mRNA expression in the ALL CR group was significantly reduced compared with the newly-diagnosed ALL group (P＜0.01). Children with a poor prognosis had significantly higher ZFX mRNA levels at diagnosis than those with a good prognosis (P＜0.05). CONCLUSIONS: ZFX is over-expressed in children with B-ALL and its levels are higher in those with a poor prognosis than those with a good prognosis, which suggests that ZFX is important in the prognosis evaluation of B-ALL.