慢性淋巴细胞白血病患者脂蛋白酯酶和血清胸苷激酶水平及其与其他预后因素的相关性研究

Lipoprotein lipase and serum thymidine kinase level in chronic lymphocytic leukemia and their corre- lations with other prognostic factors

目的探讨慢性淋巴细胞白血病（CLL）患者脂蛋白酯酶（LPL）和血清胸苷激酶（TK）水平及其与其他CLL预后因素的相关性。方法采用RT—PCR方法榆测58例CLL患者外周血标本中LPL的表达水平；增强化学发光法（ECL）和TKI单克隆抗休检测39例CLL患者外周血血清标本中TK1浓度；多重PCR及序列测定检测IgVH基因突变；流式细胞术检测ZAP-70蛋向及CD38的表达；组合探针荧光原位杂交（FISH）技术检测分子遗传学异常。结果CLL患存LPL中位表达水平为0．26（0～6．29），而在正常对照巾均未检测到LPL表达。LPL表达水平与IgVH基因突变、Binet分期、CD38表达和遗传学异常具有显著相关性，无IgVH突变患者的LPL表达水平明显高于突变患者（P=0．010）；BinetA期患者LPL表达水平低于Binet B期和C期患者（P=0．011）；CD38高表达组（≥30％）LPL表达水平高于CD38低表达组（〈30％）（P=0．001）；分子遗传学预后较好组[仅有del（13q14）]LPL表达水平明晁低于预后较差组[del（17p13）或del（11q22）]（P=0．002）。LPL表达水平与患者性别、年龄及ZAP-70蛋白表达水平均无明显卡相关性（P〉0．05）。CLL患者血清TK1浓度明显高于正常对照（P〈0．05）。在外周血淋巴细胞绝对计数（ALC）明显增高组（≥50×10^9／L）、血清乳酸脱氢酶（LDH）高水平组、无IgVH基凶突变组和ZAP-70蛋白高表达组（≥20％）的患者中，血清TK1浓度分别明显高于ALC无明显增高组（〈50×10^9／L）（P=0．018）、血清LDH水平正常组（P=O．018）、具有IgVH基因突变绀（P=0．030）和ZAP-70蛋白低表达组（〈20％）（P=0．038）的患者。血清TK1浓度与CLL患者性别、年龄、Binet分期、CD38表达水平和遗传学异常无明显相关性（P〉0．05）。结论CLL患者LPL和血清TK1表达水平与CLL其他预后因素相关，两者均对IgVH突变情况有一定预示作用，在CLL的预肟中具有再要价值。

Objective To investigate lipoprotein l ipase （LPL） and serum thymidine kinase （, TK） levels in chronic lymphocytic leukemia （CLL） and their correlations with other prognostic factors. Methods LPL expression level in peripheral blood samples of 58 CLL patients was detected by semi-quantitative re- verse transcription PCR （RT-PCR）. Serum TK1 level in 39 CLL patients was detected by enhanced chemilu- minescence （ECL） and TK monoclonal antibody （Anti-TK mAb）. IgVH mutation status was detected by multiplex PCR and sequencing of purified PCR products. The expression of ZAP-70 protein and CD38 were determined by flow eytometry . Panel probes and fluorescence in situ hybridization （FISH） were used to detect cytogenetie aberrations. Results The median LPL expression level in CLL was 0.26 （0 - 6.29）, while undeteetable in normal controls. LPL expression level was significantly correlated with IgVH mutation status, Binet stages, CD38 and cytogenetic aberrations. Patients with unmutated IgVH genes had higher LPL than those with lgVH mutations （P =0. 010）. Patients in Binet stage B and C had higher LPL than those in stage A （P=0.011）. LPL level was higher in patients with CD38≥30% （P =0. 001 ）. Higher LPL level was found in patients with unfavorable cytogenetic aberrations （deletion in 17p13 or 11 q22） than those with fa- varable cytogenetics （deletion in 13q as the sole abnormality） （P = 0. 002）. LPL level was not significantly correlated with sex, age, and ZAP-70 protein （ P 〉 0.05）. The level of TK1 was higher in CLL patients than that in normal control （P 〈 0.05 ）. Patients with higher level of absolute lymphocyte count （ ALC）, lactate dehydrogenase （LDH） , unmutated IgVH genes and ZAP-70 had higher levels of TK1 than those with lower level of ALC, LDH, mutated IgVH genes and ZAP-70 （ P = 0. 018, P = 0. 018, P = 0. 030 and P = 0. 038, respectively）. TK1 level had no correlationship with sex, age, Binet stages, CD38, and cytogenetie aberrations （P 〉 0.05）. Conclusions LPL expression and serum TK1 levels significantly correlate with other CLL prognostic factors and could be predictive markers for IgVH mutation status. LPL and serum TKI might be applied to the assessment of prognosis in CLL patients.