INTRODUCTION SLIT-ROBO is a ligand-receptor family of neuronal guidance cues that has been involved in pathological and physiological angiogenesis. SLIT-ROBO expression is altered in many tumours. However, no data exist about the role of the whole family in acute myelogenous myeloid leukemia (AML). PURPOSE Herein, we assessed the expression of all SLIT-ROBO family in bone marrow (BM) biopsy of AML patients and control group on both protein and RNA levels. METHODS The paraffin-embedded tissue blocks were subjected to immunohistochemistry for SLIT1, SLIT2, SLIT3, ROBO1, ROBO2, ROBO3, and ROBO4. Microvessel density (MVD) was evaluated by CD34 immunohistochemistry. An in silico analysis using The Cancer Genome Atlas data repository was conducted for assessment of RNA level. RESULTS Acute myeloid leukemia patients were generally high expressers of ROBO1 and ROBO2 compared to the controls (p < 0.0001, p < 0.001, respectively). In contrast, low expression of SLIT1, SLIT2, and SLIT3 ligands has been noted more commonly in AML than in control BM samples (p < 0.0001, p = 0.003, and p = 0.001, respectively). ROBO4 expression correlated with MVD. The in silico analysis showed a poor prognostic value of high ROBO3 and low SLIT2 RNA levels (p = 0.0003 and p = 0.0008, respectively), as well as high ROBO3 and ROBO4 RNA levels in cytogenetic poor risk groups of patients (p = 0.0029 and p = 0.0003, respectively). CONCLUSIONS These data indicate that SLIT-ROBO family members play a role in the biology of AML. Low expression of SLIT in BM of AML patients may suggest its expression alterations in AML. Increased expression of ROBO1 and ROBO2 in AML patients suggests their participation in AML pathogenesis.

中文翻译：

---

SLIT-ROBO家族在成人急性髓系白血病患者中的表达。


简介 SLIT-ROBO 是神经元引导信号的配体受体家族，参与病理和生理血管生成。 SLIT-ROBO 表达在许多肿瘤中发生改变。然而，尚无关于整个家族在急性髓细胞性白血病 (AML) 中的作用的数据。目的在此，我们评估了 AML 患者和对照组骨髓 (BM) 活检中所有 SLIT-ROBO 家族在蛋白质和 RNA 水平上的表达。方法对石蜡包埋的组织块进行SLIT1、SLIT2、SLIT3、ROBO1、ROBO2、ROBO3和ROBO4的免疫组织化学检测。通过 CD34 免疫组织化学评估微血管密度 (MVD)。使用癌症基因组图谱数据存储库进行计算机分析以评估 RNA 水平。结果 与对照组相比，急性髓系白血病患者通常是 ROBO1 和 ROBO2 的高表达者（分别为 p < 0.0001、p < 0.001）。相反，SLIT1、SLIT2 和 SLIT3 配体的低表达在 AML 中比在对照 BM 样本中更常见（分别为 p < 0.0001、p = 0.003 和 p = 0.001）。 ROBO4 表达与 MVD 相关。计算机分析显示，高 ROBO3 和低 SLIT2 RNA 水平（分别为 p = 0.0003 和 p = 0.0008）以及高 ROBO3 和 ROBO4 RNA 水平在细胞遗传学低风险患者组中的预后价值较差（p = 0.0029 和 p = 0.0029）。 p = 0.0003，分别）。结论 这些数据表明 SLIT-ROBO 家族成员在 AML 生物学中发挥作用。 SLIT在AML患者的BM中的低表达可能提示其在AML中的表达改变。 AML 患者中 ROBO1 和 ROBO2 表达增加表明它们参与了 AML 发病机制。