Investigation of MEG3 and WT1 polymorphisms in patients with acute myeloid leukemiaAcute myeloid leukemia (AML) is lethal hematologic malignant disorder Related to myeloid progenitor cells in bone marrow and peripheral blood. It is one of the most commonly occurring acute leukemia in adults that its incidence increases with advanced age. Multiple environmental and genetical factors can cause AML.
Genetic factors including large chromosomal translocation that is common in AML, result in gene rearrangements and point mutations, amplifications, deletions found in AML.Recent reports have suggested that Long noncoding RNAs (lncRNAs) is involved in various cancers and also in AML. During the recent studies, it was found that lncRNAs as a new regulator for the expression of proto-oncogenes or tumor suppressor genes In a variety of cancers. LncRNAs are greater than 200 nucleotides and are noncoding single strand RNA that has no protein production capacity. lncRNAs play important roles in apoptosis, cell cycle, imprinting, epigenetic regulation, transcription, translation, the regulation of gene expression, chromatin remodeling, cell differentiation, and development.One of several lncRNA genes involved in AML disease is Maternally expressed gene 3. (MEG3) is a cancer-related lncRNA and located on chromosome14 q32.
3 in humans.MEG3 expresses in some normal tissues and decreases or losses in many human cancers. MEG3 Overexpression could promote apoptosis and inhibit proliferation in tumor cells.Previous studies suggested that MEG3 functions as a tumor suppressor through activating p53 pathway.It has been proven that WT1 activates MEG3.
Therefore a novel target of the WT1 gene is MEG3.The WT1 (Wilms’ tumor) is located at chromosome 11p13 and encodes a zinc ?nger protein, that is a transcription factor. WT1 plays important role in cell growth, development and differentiation. Recently, it has been shown that the WT1 gene, in addition to the role of a tumor suppressor, plays an important role in oncogenicity.
WT1 commonly expressed in some tissues including the uterus, gonads, immature cells in bone marrow, mesothelial lining of the gut, spleen, kidney and, to progenitor cells in various types of tissues, heart-lung.overexpression of WT1 has been seen in AML patients and various types of solid tumors.mutations or epigenetic silencing could dysregulation of WT1 and that is causally involved in AML. According to recent studies, we anticipate that genetic variants of MEG3 and WT1 may modify the development of AML. To test our prediction we perform AML case-control study comprising 40 patients and 40 control subjects from Iran. lthough a number of studies suggested that WT1rs16754 polymorphism might be relatedto decreased relapse-free survival (RFS) and overall survival (OS The results remain controversial 7-18. In this study meta-analysis of the association between WT1 rs16754 polymorphism and OS and RFS of AML was conducted Twelve studies involving 3903 patients with AML are pooled in the meta-analysishotspot in exon 7, also the location of SNP rs16754. In a study of 249 adult patients with normal-karyotype AML, Damm et al reported that SNP rs16754independently predicted improved overall survival (OS) and relapse-free survival (RFS) in adult AML.
In our study, we deter mined the prevalence of SNP rs16754 in a large cohort of pediatric AML patients enrolled on three consecutive CCG/COG trials. We then analyzed biologic or clinical differences among SNP-positive and SNP-negative patients and examined the prognostic signi?cance of harboring at least one copy of the minor SNP allele in the context of other previously validated risk factors in pediatric AML