Department of Hematology, Yixing People's Hospital, Yixing, China. staff151yxph.com.
Eur Rev Med Pharmacol Sci. 2020 May;24(10):5564-5572. doi: 10.26355/eurrev_202005_21342.
Acute lymphoblastic leukemia (ALL) causes the dysfunction of the systemic blood system and immune system. The etiology and predisposing factors of ALL are unknown. The suppressor of cytokine signaling 1 (SOCS1) and SOCS2 are inhibitors of cytokine signal transduction. Gene polymorphisms of SOCS1 and SOCS2 and their expressions may be related to ALL.
A total of 200 ALL patients in our hospital and 200 healthy people were enrolled in ALL group and control group, respectively. Genomic deoxyribonucleic acids (DNAs) and total RNAs were extracted from the peripheral blood of each subject. Gene polymorphisms of SOCS1 at rs33977706, rs243327, and rs33932899 and those of SOCS2 at rs3816997 were amplified by polymerase chain reaction (PCR) and sequenced. Besides, the expression levels of SOCS1 and SOCS2 in ALL patients were detected by real-time fluorescence quantitative PCR.
The frequency of the allele C of SOCS1 rs33977706 in ALL group was lower than that in the control group, displaying a significant difference between the two groups (p=0.015). The frequency of allele A of SOCS2 rs3816997 was notably higher in ALL group than that of the control group (p=0.000). In addition, the frequency of CA genotype of SOCS1 rs33977706 in ALL group was markedly lower than that in the control group, showing a significant difference (p=0.000). ALL group had remarkably higher frequencies of AA genotype of SOCS2 rs3816997 (p=0.000) and ACC haplotype of SOCS gene (p=0.000), and lower frequencies of ATG (p=0.026) and CCC (p=0.006) haplotypes. The two loci, SOCS1 rs33932899 and SOCS1 rs243327, were linked to each other (D'=0.781). Moreover, the expression level of SOCS1 in ALL group was lower than that in the control group, in which the expression of the CT genotype of SOCS1 rs243327 was relatively higher (p=0.021). SOCS2 level was lower in ALL group. Particularly, SOCS2 level in ALL patients carrying AC genotype was lower than those carrying AA and CC genotypes (p=0.000). ALL patients carrying CT genotype of SOCS1 rs243327 had shorter period of agranulocytosis (p=0.000), a lower ratio of bone marrow primitive/immature cells (p=0.001), and a higher hemoglobin (Hb) level in blood (p=0.000). The ratio of bone marrow primordial/immature cells was lower in ALL patients with AC genotype of SOCS2 rs3816997 (p=0.038).
The expression levels of SOCS1 and SOCS2 are prominently related to ALL, and their polymorphisms are associated with the susceptibility to ALL.
急性淋巴细胞白血病（ALL）导致全身血液系统和免疫系统功能障碍。ALL 的病因和易患因素尚不清楚。细胞因子信号转导抑制因子 1（SOCS1）和 SOCS2 是细胞因子信号转导的抑制剂。SOCS1 和 SOCS2 的基因多态性及其表达可能与 ALL 有关。
将我院收治的 200 例 ALL 患者和 200 例健康人分别纳入 ALL 组和对照组。从每位受试者的外周血中提取基因组脱氧核糖核酸（DNA）和总 RNA。采用聚合酶链反应（PCR）和测序法扩增 SOCS1 基因 rs33977706、rs243327 和 rs33932899 及 SOCS2 基因 rs3816997 的基因多态性。此外，采用实时荧光定量 PCR 检测 ALL 患者 SOCS1 和 SOCS2 的表达水平。
ALL 组 SOCS1 rs33977706 等位基因 C 的频率低于对照组，两组间差异有统计学意义（p=0.015）。ALL 组 SOCS2 rs3816997 等位基因 A 的频率明显高于对照组（p=0.000）。此外，ALL 组 SOCS1 rs33977706 的 CA 基因型频率明显低于对照组，差异有统计学意义（p=0.000）。ALL 组 SOCS2 rs3816997 的 AA 基因型（p=0.000）和 SOCS 基因 ACC 单倍型（p=0.000）频率显著升高，而 ATG（p=0.026）和 CCC（p=0.006）单倍型频率显著降低。SOCS1 rs33932899 和 SOCS1 rs243327 两个位点相互连锁（D'=0.781）。此外，ALL 组 SOCS1 的表达水平低于对照组，其中 SOCS1 rs243327 的 CT 基因型表达相对较高（p=0.021）。SOCS2 水平在 ALL 组中较低。特别是，携带 SOCS2 rs3816997AC 基因型的 ALL 患者的 SOCS2 水平低于携带 AA 和 CC 基因型的患者（p=0.000）。携带 SOCS1 rs243327 CT 基因型的 ALL 患者粒细胞缺乏症的持续时间较短（p=0.000），骨髓原始/幼稚细胞比例较低（p=0.001），血液中血红蛋白（Hb）水平较高（p=0.000）。携带 SOCS2 rs3816997AC 基因型的 ALL 患者骨髓原始/幼稚细胞比例较低（p=0.038）。
SOCS1 和 SOCS2 的表达水平与 ALL 显著相关，其多态性与 ALL 的易感性有关。
