β整合素家族在儿童急性T淋巴细胞白血病的表达及其临床意义

Expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia

摘要:

目的 探讨β整合素家族成员在儿童急性T淋巴细胞白血病（T-ALL）的表达及临床意义。方法 收集22例初诊T-ALL患儿和21例对照（非恶性血液病患者和骨髓移植供者）的骨髓标本，采用实时荧光定量PCR方法，检测β整合素家族各成员的mRNA表达；并利用整合素抑制剂精氨酸-甘氨酸-天冬氨酸（RGD）肽作用于Jurkat细胞，采用CCK 8法和流式细胞术检测Jurkat细胞生存率和凋亡情况。结果 与对照组相比，T-ALL患儿的整合素β₂、β₃、β₅的mRNA表达水平显著下调（P < 0.05）。在外周血白细胞计数< 100×10⁹/L、第33天骨髓不缓解或MRD阳性的T-ALL患儿中，整合素β₃表达水平较高（P < 0.05）；复发T-ALL患儿整合素β₅的表达高于无复发T-ALL患儿（P < 0.05）。整合素β₃高表达T-ALL患儿的EFS率、OS率均低于β₃低表达者（P < 0.05）。与未处理组比较，RGD肽处理的Jurkat细胞生存率较低、凋亡率均高（P < 0.05）。结论 β整合素可能通过影响细胞的增殖和凋亡而影响T-ALL的发生发展，整合素β₅的表达与T-ALL复发风险密切相关，整合素β₃的表达与T-ALL患儿治疗反应及预后密切相关。

Abstract:

Objective To study the expression of β-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance. Methods Quantitative real-time PCR analyses were performed to assess the expression levels of β-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively. Results The mRNA levels of integrins β₂, β₃, and β₅ were significantly lower in children with T-ALL than in controls (P < 0.05). In T-ALL patients, high integrin β₃ expression was associated with lower white blood cell counts (< 100×10⁹/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P < 0.05). In T-ALL patients, higher integrin β₅ expression was associated with relapse of T-ALL (P < 0.05). Based on survival curve analysis, higher integrin β₃ expression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P < 0.05). Conclusions β-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin β₅ is closely related to the risk of relapse of T-ALL. The expression of integrin β₃ is closely related the treatment response and prognosis of T-ALL.