Al-Kuraishy Hayder M, Al-Gareeb Ali I, Al-Buhadilly Ali K
Department Of Pharmacology, Toxicology, and Medicine, College of Medicine Al-mustansiriyah University, P.O. Box 14132 Baghdad, Iraq.
Diseases. 2018 Jan 25;6(1):13. doi: 10.3390/diseases6010013.
The p53 gene is also known as tumor suppressor p53. The main functions of the p53 gene are an anticancer effect and cellular genomic stability via various pathways including activation of DNA repair, induction of apoptosis, and arresting of cell growth at the G1/S phase. Normally, the p53 gene is inactivated by mouse double minute 2 proteins (mdm2), but it is activated in chronic myeloid leukemia (CML). Tyrosine kinase inhibitors are effective chemotherapeutic agents in the management of CML. The purpose of the present study was to evaluate the differential effect of imatinib and nilotinib on p53 gene serum levels in patients with CML. A total number of 60 patients with chronic myeloid leukemia with ages ranging from 47 to 59 years were recruited from the Iraqi Hematology Center. They started with tyrosine kinase inhibitors as first-line chemotherapy. They were divided into two groups-Group A, 29 patients treated with imatinib and Group B, 31 patients treated with nilotinib-and compared with 28 healthy subjects for evaluation p53 serum levels regarding the selective effect of either imatinib or nilotinib. There were significantly ( < 0.01) high p53 gene serum levels in patients with CML (2.135 ± 1.44 ng/mL) compared to the control (0.142 ± 0.11 ng/mL). Patients with CML that were treated with either imatinib or nilotinib showed insignificant differences in most of the hematological profile ( > 0.05) whereas, p53 serum levels were high (3.22 ± 1.99 ng/mL) in nilotinib-treated patients and relatively low (1.18 ± 0.19 ng/mL) in imatinib-treated patients ( = 0.0001).
Nilotinib is more effective than imatinib in raising p53 serum levels in patients with chronic myeloid leukemia.
p53基因也被称为肿瘤抑制因子p53。p53基因的主要功能是通过多种途径发挥抗癌作用并维持细胞基因组稳定性，这些途径包括激活DNA修复、诱导细胞凋亡以及使细胞生长停滞在G1/S期。正常情况下，p53基因被小鼠双微体2蛋白（mdm2）灭活，但在慢性髓性白血病（CML）中它会被激活。酪氨酸激酶抑制剂是治疗CML的有效化疗药物。本研究的目的是评估伊马替尼和尼洛替尼对CML患者p53基因血清水平的不同影响。从伊拉克血液学中心招募了60例年龄在47至59岁之间的慢性髓性白血病患者。他们开始接受酪氨酸激酶抑制剂作为一线化疗。患者被分为两组——A组，29例接受伊马替尼治疗；B组，31例接受尼洛替尼治疗——并与28名健康受试者进行比较，以评估伊马替尼或尼洛替尼的选择性作用对p53血清水平的影响。与对照组（0.142±0.11 ng/mL）相比，CML患者的p53基因血清水平显著升高（<0.01，2.135±1.44 ng/mL）。接受伊马替尼或尼洛替尼治疗的CML患者在大多数血液学指标上差异不显著（>0.05），然而，尼洛替尼治疗的患者p53血清水平较高（3.22±1.99 ng/mL），而伊马替尼治疗的患者相对较低（1.18±0.19 ng/mL）（P = 0.0001）。
在提高慢性髓性白血病患者的p53血清水平方面，尼洛替尼比伊马替尼更有效。
