Nemes Karolina, Csóka Monika, Nagy Noémi, Márk Ágnes, Váradi Zsófia, Dankó Titanilla, Kovács Gábor, Kopper László, Sebestyén Anna
2nd Department of Pediatrics, Semmelweis University, Budapest, 1094, Tűzoltó u. 7-9., Hungary.
Pathol Oncol Res. 2015 Jul;21(3):597-604. doi: 10.1007/s12253-014-9861-z. Epub 2014 Nov 12.
In spite of the improved efficacy of therapy, it still fails in 15-20 % of childhood acute lymphoblastic leukemia (ALL) patients. Recently, altered expression of certain miRNAs (miRs) have been described in ALL with potential effect on prognosis. Presence of certain miRs (miRNA-16, -21, -24, -29b, -128b, -142-3p, -155, -223) was characterized in human lymphoma and leukemia cells by real-time PCR. Expression of miRs in pediatric ALL patients (n = 24) was measured before chemotherapy, at conventional response checkpoints and at relapse. Correlation between altered miR expression and response to prednisolone at day 8 of therapy and long term prognosis was statistically analysed. Overexpression of "oncomiR/inflammamiR"-21 - which is characteristic in different tumors-was missing in human ALL cells. However, higher expression of miR-128b and lower expression of miR-223 is generally characteristic for human ALL cell lines and ALL cells isolated from pediatric patients. Correlation was shown between miR-128b expression and prognosis, prednisolone response and survival data in childhood ALL. Expression of miR-128b and miR-223-both are leukemia specific-changed in parallel with percentage of bone marrow blasts in remission and during relapse. Therefore, we suggest that overexpression of miR-128b and downregulation of miR-223 shows a significant correlation with treatment response and prognosis in childhood ALL.
尽管治疗效果有所改善，但仍有15%-20%的儿童急性淋巴细胞白血病（ALL）患者治疗失败。最近，已在ALL中描述了某些微小RNA（miR）表达的改变，其对预后具有潜在影响。通过实时PCR对人淋巴瘤和白血病细胞中某些miR（miRNA-16、-21、-24、-29b、-128b、-142-3p、-155、-223）的存在情况进行了表征。在化疗前、常规反应检查点和复发时测量了儿科ALL患者（n = 24）中miR的表达。对治疗第8天miR表达改变与泼尼松龙反应及长期预后之间的相关性进行了统计学分析。在人ALL细胞中不存在不同肿瘤中具有特征性的“致癌miR/炎症miR”-21的过表达。然而，miR-128b的较高表达和miR-223的较低表达通常是人ALL细胞系和从儿科患者分离的ALL细胞的特征。在儿童ALL中显示了miR-128b表达与预后、泼尼松龙反应及生存数据之间的相关性。miR-128b和miR-223（两者均为白血病特异性）的表达与缓解期和复发期骨髓原始细胞百分比平行变化。因此，我们认为miR-128b的过表达和miR-223的下调与儿童ALL的治疗反应和预后显著相关。
