EVALUATION OF P14ARF, P27KIP1 AND P21CIP1, CELL CYCLE REGULATORY GENES, EXPRESSION IN ACUTE MYELOID LEUKEMIA PATIENTS

Abstract

Objective: Acute myeloid leukemia (AML) is an excessive proliferation of immature malignant myeloid progenitors essentially affected by cell cycle abnormalities. Generally, cell cycle is tightly regulated by cyclin, cyclin-dependant kinases (CDKs) and CDK inhibitors (CDKIs). Their defects can result in abnormal proliferation of leukemic cells. Since P14ARF, P27kip1, P21Cip1, and CDKIs, traditionally have a crucial role in cell cycle regulation and they have been reported to be frequently involved in human tumor initiation and progression, we aimed to evaluate the expression of these genes in patients with de novo AML. Patients and Methods: In this case-control study, quantitative Real-time PCR was used to rate P14, P27 and P21 expression levels in bone marrow and peripheral blood samples of 93 newly diagnosed AML patients (39 male and 54 female) and 13 healthy people (8 male and 5 female) as the control group. Data were analyzed via SPSS16 software and p<0.05 was designated as the significant level. Results: Our results revealed that P14 and P27 are overexpressed in patients with AML compared to the control group (p<0.05). However, there was no significant change in P21 expression in our patients in comparison with control group. In addition, a significant and positive correlation was observed between expression of these genes in AML patients (p<0.0001, r=0.359, for P14 and P27, p<0.0001, r=0.674 for P14 and P21, p<0.0001, r=0.501, for P27 and P21). Conclusions: Our study indicated P14 and P27 overexpression in AML patients. Although CDKIs down regulation clearly indicates their inability to guard cells against cancer, it is completely difficult to justify their overexpression as it can be a part of normal reaction of cells against malignant process or can indicate their functional switch in favor of malignant process. However, recent studies support the second hypothesis strongly.