B-cell acute lymphoblastic leukemia (B-ALL) accounts for nearly one fifth of all childhood cancers and current challenges in B-ALL treatment include resistance, relapse and late-onset side effects due to the chemotherapy. To overcome these hurdles, novel therapies need to be investigated. One promising target is Polo-like kinase 1 (Plk1), a key regulator of the cell cycle. In this study, the Plk family expression is investigated in primary peripheral blood and bone marrow mononuclear cells from ten pediatric B-ALL patients. For the first time, short interfering RiboNucleic Neutrals (siRNNs) that enter cells without a transfection reagent are used to target Plk1 mRNA in primary cells from pediatric B-ALL patients. Our results show that the expression of Plk1 and Plk4 is significantly higher in pediatric B-ALL patients compared to healthy donors. Moreover, treatment of primary peripheral blood and bone marrow mononuclear cells from pediatric B-ALL patients, cultured ex vivo, with Plk1-targeting siRNNs results in cleavage of Plk1 mRNA. Importantly, the Plk1 knockdown is specific and does not affect other Plk members in contrast to many small molecule Plk1 inhibitors. Thus, Plk1 is a potential therapeutic target in pediatric B-ALL and selective targeting of Plk1 can be achieved by the use of siRNNs.

B 细胞急性淋巴细胞白血病 (B-ALL) 占所有儿童癌症的近五分之一，目前 B-ALL 治疗面临的挑战包括化疗引起的耐药性、复发和迟发性副作用。为了克服这些障碍，需要研究新的疗法。一个有希望的靶点是 Polo 样激酶 1 (Plk1)，它是细胞周期的关键调节因子。在这项研究中，研究了 10 名儿童 B-ALL 患者的原代外周血和骨髓单核细胞中的 Plk 家族表达。首次使用无需转染试剂即可进入细胞的短干扰核糖核酸中性 (siRNN) 来靶向儿科 B-ALL 患者原代细胞中的 Plk1 mRNA。我们的结果表明，与健康供体相比，儿童 B-ALL 患者中 Plk1 和 Plk4 的表达显着较高。此外，用 Plk1 靶向 siRNN 处理离体培养的儿童 B-ALL 患者的原代外周血和骨髓单核细胞，会导致 Plk1 mRNA 裂解。重要的是，与许多小分子 Plk1 抑制剂相比，Plk1 敲低是特异性的，不会影响其他 Plk 成员。因此，Plk1 是儿科 B-ALL 的潜在治疗靶点，并且可以通过使用 siRNN 来实现 Plk1 的选择性靶向。