DNA ploidy and expression of P53, cMyc in childhood leukemia's and their families

ABSTRACT

Chromosomal abnormalities in childhood leukemia have important biological, diagnostic and prognostic significance. The genes that are associated with the development of malignancy were categorized as oncogenes and tumor suppressor genes. P53 belongs to the category of tumor genes and is located on the short arm of chromosome 17 p13. It is a specific transcriptional activator of genes controlling GI checkpoint of the cell cycle and controls the expression of certain genes involved in the control of programmed cell death [Apoptosis]. cMyc gene is Juxtaposed with one of the immunoglobulin genes heavy chain on 14[q32], kappa on 2[p12] or Iambda on 22[q11]. In pediatric ALL with translocation of ch.,8 [q24] onch., 14[q32] or ch22[q11], c-Myc expression is markedly deregulated by the highly active immunoglobulin locus. This leads to an increase in c-Myc max dimmers and transactivation of multiple cognate target genes, driving uncontrolled cellular proliferation. This study was designed to determine the DNA content [ploidy], expression P53 protein and c-Myc protein in children with acute lymphoblastic leukemia as well as in their first degree relatives [parents and siblings] in order to detect the role of these proteins in the developing of leukemia and those at risk of developing leukemia This study was done on 20 infants and children [16 males and 4 females], their age ranged from 2 to 12 years. They were admitted to the Hematology Unit at Mansoura University Children Hospital where they were diagnosed as acute lymphoblastic leukemia [ALL] and were taken at presentation before induction of treatment. Their first-degree relatives were also included in the study [20 fathers, 20 mothers and 44 siblings [23 brothers and 21 sisters]].Twenty healthy persons with negative family /history of cancers, their aye range from 4 to 30 years, were taken as control group. All the studied subjects were subjected to isolation of lymphocyte which staining and fixation within 24 hours from sampling where DNA analysis by flow cytometer was done. The results proved that 60 % of the cases with acute lymphoblastic leukemia were hyper diploid [DWA index >1.0] and 10 % were hypo diploid [DNA index [1.0]. All of their leukemic children were DNA aneuploid while 10 % of tile-studied parents had DNA aneuploid positive cells and 7% of the healthy siblings had DNA aneuploid positive cells. A high significant level of p53 protein in patients with ALL when compared with healthy controls [p<0.0001], a significant difference in between patients with ALL and their first -degree relative regarding P53 protein. Also a significant difference in between the first-degree relative and healthy controls regarding p53 [p=<0.0001]. The results of this study also showed significant difference in the level of expression of p53 protein among patients with DNA aneuploidy cells compared to those with DNA diploid patients. A significant difference in patients with ALL when compared with healthy controls, also were was significant difference in first degree relatives of leukemia patients versus to healthy controls regarding the level of c-Myc protein [p=<0.0001]. 80 % of parents and 77 % of siblings between the first-degree relative expressing high levels of cMyc protein