Farahat Nahla Mohamed Gamal, Elkaffash Dalal Mohamed Nasr El Din, Alghandour Ashraf Hussein, Swelem Rania Shafik, Abo El-Wafa Reham Abdel Haleem
1Clinical and Chemical Pathology Department, Faculty of Medicine, Alexandria University, Khartoum Square, El Sultan Hussein Street, Azarita, Alexandria 21131 Egypt.
2Internal Medicine (Hematology), Faculty of Medicine, Alexandria University, Azarita, Alexandria Egypt.
Indian J Hematol Blood Transfus. 2019 Jan;35(1):89-99. doi: 10.1007/s12288-018-1000-7. Epub 2018 Aug 3.
MicroRNAs target mRNAs for cleavage or translational repression. They play a critical role in the progression of malignancies and leukemias including chronic lymphocytic leukemia (CLL). However, microRNA expression levels in Egyptian patients with CLL, and their prognostic value remain elusive. Our main aim was to assess the expression pattern of a panel of microRNAs in CLL patients to create an informative microRNA profile. The study subjects were 40 newly diagnosed CLL patients of both sexes and 40 age and sex matched controls. The expression levels of 12 microRNAs were evaluated by qRT-PCR, including miR-15a, 16, 23b, 24, 29a, 29c, 34a, 146a, 155, 181a, 195, and 221. Flow cytometry was used to determine the expression levels of BCL2, CD38, and ZAP-70 in CLL patients. We identified various degrees of upregulated miRNAs (miR-29a, miR-29c, miR-34a, miR-155, miR-146a, and miR-195) and down-regulated ones (miR-15a, miR-16, miR-23b, miR-24, miR-181a, and miR-221) in CLL patients relative to controls. The mean fluorescence intensity ratio (MFI-R) of BCL2 was recorded and was significantly upregulated in CLL patients compared with normal controls. In addition, inverse correlations were observed between microRNAs (miR-15a, miR-16, miR-155, and miR-195) and BCL2 MFI-R while positive correlations were observed between miR-29a and miR-29c, and BCL2 MFI-R. These findings suggest that these miRNAs regulate levels. Moreover, we found that miR-15a, miR-16, miR-155, miR-181a, miR-195 and miR-221 were significantly upregulated, while miR-29a and miR-29c were significantly downregulated in ZAP-70 positive CLL patients. Various miRNAs may play an important role in the pathogenesis of CLL and have the potential to be used for the prognosis of patients with CLL.
微小RNA作用于信使核糖核酸以进行切割或翻译抑制。它们在包括慢性淋巴细胞白血病（CLL）在内的恶性肿瘤和白血病进展中发挥关键作用。然而，埃及CLL患者的微小RNA表达水平及其预后价值仍不明确。我们的主要目的是评估一组微小RNA在CLL患者中的表达模式，以建立一个有信息量的微小RNA谱。研究对象为40例新诊断的CLL患者（男女均有）以及40例年龄和性别匹配的对照。通过qRT-PCR评估12种微小RNA的表达水平，包括miR-15a、16、23b、24、29a、29c、34a、146a、155、181a、195和221。采用流式细胞术测定CLL患者中BCL2、CD38和ZAP-70的表达水平。我们发现，与对照组相比，CLL患者中存在不同程度上调的微小RNA（miR-29a、miR-29c、miR-34a、miR-155、miR-146a和miR-195）以及下调的微小RNA（miR-15a、miR-16、miR-23b、miR-24、miR-181a和miR-221）。记录了BCL2的平均荧光强度比值（MFI-R），与正常对照组相比，CLL患者中该比值显著上调。此外，观察到微小RNA（miR-15a、miR-16、miR-155和miR-195）与BCL2 MFI-R之间呈负相关，而miR-29a和miR-29c与BCL2 MFI-R之间呈正相关。这些发现表明这些微小RNA调节水平。此外，我们发现ZAP-70阳性的CLL患者中miR-15a、miR-16、miR-155、miR-181a、miR-195和miR-221显著上调，而miR-29a和miR-29c显著下调。各种微小RNA可能在CLL的发病机制中起重要作用，并有可能用于CLL患者的预后评估。
