Evaluation of P21Cip1 and P27Kip1 expression in de novo acute lymphoblastic leukemia patients

Abstract

Background: Acute lymphoblastic leukemia (ALL) arises from an imbalanced proliferation and differentiation of lymphoid progenitors due to special chromosomal and epigenetic abnormalities affecting cell cycle regulation. The cyclin-dependent kinase inhibitor (CDKI) family has crucial functions in G1 progression and G1 to S entry regulation. Among CDKIs, P21 and P27 are able to exert remarkable effects on all CDKs. Hence, we investigated the expression levels of P21 and P27 in ALL patients to determine whether or not their expression had been altered.

Materials and Methods: In the present study, we evaluated P21 and P27 expression in bone marrow and peripheral blood samples of 52 newly diagnosed ALL patients (30 males, 22 females) and 13 healthy normal controls (5 males, 8 females) using quantitative real-time PCR. Data were analyzed via SPSS (version 16) software and P<0.05 was assigned as the statistical significance level.

Results: Our findings demonstrated lower expression levels of P21 and P27 in ALL patients compared with normal controls (8.33- and 1.69-fold change, respectively). P21 and P27 expression was significantly different between T-cell acute lymphoblastic leukemia (T-ALL) and B-cell acute lymphoblastic leukemia (B-ALL) patients (P= 0.03).

Conclusion: Since P21 and P27 are able to influence the activity of both cyclins and CDKs, it is postulated that decreased expression of these genes reduces P21- and P27- mediated suppressive effects on cyclins and CDKs. Therefore, these events facilitate the activation of cyclins and CDKs which may result in cancer progression in ALL patients.