Haematology Unit, Mansoura University Oncology Centre.
Paediatric Department, Paediatric Haematology Oncology Unit.
J Pediatr Hematol Oncol. 2021 Aug 1;43(6):e798-e803. doi: 10.1097/MPH.0000000000002010.
The role of cortactin in T-cell acute lymphoblastic leukemia (T-ALL) tissue infiltration has been previously reported. However, its impact on patients' responsiveness to therapy and patient's outcome was not previously addressed. This study was conducted on 60 T-ALL pediatric patients at diagnosis and 10 nonleukemic controls. Cortactin and HS1 expressions were identified by real-time polymerase chain reaction. Cortactin and HS1 expression were significantly higher in T-All patients as compared with controls as well as postinduction levels (P≤0.001 for both). The high cortactin expression was significantly associated with high peripheral white cell counts (P≤0.001), blood blast cells (P≤0.001) and central nervous system (CNS) infiltration (P≤0.001), and early precursor T-ALL subtype (P≤0.001) as compared with the remaining groups. The induction of remission response was significantly higher in T-ALL patients with lower cortactin expression levels as compared with T-ALL patients with higher one (P≤0.001). The high cortactin and HS1 expressions were significantly predictors of CNS infiltrations (hazard ratios [HR]: 1.051, confidence interval [CI]: 1.02-1.13, P=0.04 and HR: 1.87, CI: 1.23-2.091, P=0.002, respectively) and bone marrow relapse (HR: 1.43, CI: 1.18-1.92, P=0.004 and HR: 1.07, CI: 1.01-1.24, P=0.002, respectively). Furthermore, high cortactin expression levels were associated with shorter B-ALL patients' overall survival as compared with those with lower cortactin levels (P=0.002). In conclusion, high expression of cortactin and/or HS1 at diagnosis is a bad prognostic marker of T-ALL patients' outcome. Moreover, cortactin and/or HS1 expression could be used as a biomarker for refining risk stratification of T-ALL.
先前已有研究报道，衔接蛋白(cortactin)在 T 细胞急性淋巴细胞白血病（T-ALL）组织浸润中的作用。然而，其对患者对治疗的反应性和患者预后的影响此前尚未得到解决。本研究纳入了 60 例初诊 T-ALL 儿科患者和 10 例非白血病对照。通过实时聚合酶链反应鉴定衔接蛋白和 HS1 的表达。与对照组和诱导后水平相比，T-ALL 患者的衔接蛋白和 HS1 表达明显更高（均 P≤0.001）。高表达的衔接蛋白与外周白细胞计数高（P≤0.001）、血液原始细胞（P≤0.001）和中枢神经系统（CNS）浸润（P≤0.001）以及早期前体 T-ALL 亚型（P≤0.001）显著相关，而与其余组相比。与高表达组相比，低表达组的 T-ALL 患者缓解反应诱导率显著更高（P≤0.001）。高表达的衔接蛋白和 HS1 是 CNS 浸润的显著预测因子（风险比[HR]：1.051，置信区间[CI]：1.02-1.13，P=0.04 和 HR：1.87，CI：1.23-2.091，P=0.002）和骨髓复发（HR：1.43，CI：1.18-1.92，P=0.004 和 HR：1.07，CI：1.01-1.24，P=0.002）。此外，与低表达组相比，高表达组的 B-ALL 患者总生存期较短（P=0.002）。总之，初诊时高表达衔接蛋白和/或 HS1 是 T-ALL 患者预后不良的标志物。此外，衔接蛋白和/或 HS1 表达可作为 T-ALL 风险分层的生物标志物。
