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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. Abstract

Background: Acute lymphoblastic leukemia (ALL) is a malignancy of lymphoid progenitors in bone marrow, peripheral blood, and extra medullar, which accounts for 1/4 of childhood cancers. Objectives: Regarding the uncertainties of the exact causes of the disease and the importance of identifying risk factors of acute lymphoblastic leukemia, this study aimed at investigating the causes of pre-and post -natal birth in children with ALL. Methods: This case -control study was performed on 156 patients with ALL and 85 patients without ALL in a 4 -year period in Ali Asghar, Shahid Faghihi, and Shahid Motahari Hospitals in Shiraz, Iran between January 2013 and March 2017. The student's t and Chi -square tests were used. To evaluate relationships between various variables, Pearson's or Spearman's correlation analyses were used. The data were analyzed, using the SPSS 16 software. Results: Based on the findings of this study, the presence of Dawn's syndrome and familial history of leukemia and brain tumors were identified as risk factors for the incidence of ALL in children. There was no significant relationship with the history of abortion, radiation exposure, economic status, place of residence, birth rate, etc. Conclusions:The results indicate that among pre-and post -birth causes, the presence of Down syndrome and familial history of leukemia and brain tumors were as risk factors for the incidence of ALL in children. Due to the fact that therapeutic protocols are useful for the treatment of ALL in children, the results of this study and similar studies can be effective in preventing and managing the disease in children.