HIF-1α在成人急性淋巴细胞白血病患者骨髓单个核细胞中的表达及意义

Expression and significance of in bone marrow mononuclear cells of HIF-1α adult patients with ALL

摘要:

目的探讨低氧诱导因子-1α（HIF-1α）在成人急性淋巴细胞白血病（ALL）患者骨髓单个核细胞中的表达及意义。方法选取73 例成人初诊ALL患者，同期留取非白血病骨髓30 份作为对照组，采集并分离骨髓单个核细胞，利用实时荧光定量聚合酶链反应技术检测骨髓单个核细胞中HIF-1α 基因表达，利用Kaplan-Meier生存分析分析HIF-1α 基因表达对患者无复发生存时间的影响。结果成人初诊ALL患者骨髓单个核细胞中HIF-1α mRNA 相对表达量（1.86±0.18），高于对照组（1.17±0.09），差异有统计学意义（t =25.020， p=0.000）；B 系-ALL（B-ALL）和T 系-ALL（T-ALL）患者骨髓单个核细胞中HIF-1α mRNA 相对表达量均高于对照组（p <0.05），而B-ALL和T-ALL患者之间差异无统计学意义（t =0.807，p =0.211）；费城染色体（Ph）阳性和Ph 阴性患者HIF-1α mRNA 相对表达量均高于对照组（p <0.05），而Ph 阳性和Ph 阴性患者之间差异无统计学意义（t =1.314，p =0.096）；B-ALL和T-ALL成人初诊ALL患者骨髓单个核细胞中HIF-1α 信使核糖核酸（mRNA）相对表达量均与性别、年龄、白细胞水平和危险度分级无关（p >0.05）；以HIF-1α mRNA 相对表达量的P25 为截点，将患者分为低表达组（n =18）和高表达组（n =55），低表达组随访中复发4 例，复发率22.2%，高表达组随访中复发20 例，复发率36.4%，Kaplan-Meier生存分析显示，低表达组无复发生存时间11.2 个月，长于高表达组的8.6 个月，但差异无统计学意义（χ2=1.771， p=0.183）。结论HIF-1α在成人初诊ALL患者骨髓单个核细胞中呈高表达，可能与ALL患者化疗耐药及复发相关。

关键词:急性淋巴细胞白血病;成人;低氧诱导因子-1α;骨髓单个核细胞

Abstract:

Objective To investigate the expression and significance of hypoxia-inducible factor-1a(HIF-1α ) in bone marrow mononuclear cells of adult patients with acute lymphoblastic leukemia (ALL). Methods Seventy-three adult patients with newly-diagnosed ALL were selected. In the same period, 30 samples of bone marrow from non-leukemic patients were selected as the control group. Bone marrow mononuclear cells were harvested and isolated. The expression of gene in bone marrow mononuclear cell was detected by qRT-PCR. The effect of the expression of gene on the relapse-free survival time was analyzed by Kaplan-Meier. Results The relative expression level of HIF-1a mRNA in bone marrow mononuclear cells of the adult patients with newly diagnosed ALL was (1.86 ±0.18), which was significantly higher than that of the control group (1.17 ±0.09), and the difference was statistically significant (t = 25.020,p = 0.000). The relative expression levels of HIF-1α mRNA in bone marrow mononuclear cells of the patients with B-ALL and T-ALL were higher than those of the control group (p < 0.05), while there was no significant difference between those with B-ALL and T-ALL (t = 0.807, p= 0.211). The relative expression levels of HIF-1α mRNA in bone marrow mononuclear cells of Philadelphia chromosome (Ph)-positive and Ph-negative patients were higher than those of the control group (p < 0.05), while there was no significant difference between Ph-positive group and Ph-negative group ( t= 1.314,p = 0.096). The relative expression levels of HIF-1α mRNA in bone marrow mononuclear cells of the B-ALL and T-ALL patients were unrelated with sex, age, leukocyte level or risk grade ( p > 0.05). According to the cutoff value of P25 of the relative expression level of HIF-1αmRNA, the patients were divided into the low expression group (n = 18) and the high expression group ( n= 55). During the follow-up period, 4 cases in the low expression group had recurrence, the recurrence rate was 22.2%; 20 cases in the high expression group had recrudescence, the recurrence rate was 36.4%. Kaplan-Meier survival analysis showed that the relapse-free survival time in the low expression group was 11.2 months, which was longer than that of the high expression group (8.6 months), but the difference was not statistically significant (x2 = 1.771, p= 0.183). Conclusions HIF-1α is highly expressed in bone marrow mononuclear cells of adult patients with newly diagnosed ALL. It may be associated with chemotherapy resistance and recurrence.

Key words:acute lymphoblastic leukemia; adult; HIF-1α; bone marrow mononuclear cells