Acute 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)with 10 exons is located at chromosome 11p13 and encodes a zinc ?nger protein, that is a transcription factor. WT1 plays an important role an 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.WT1 protein includes an N-terminal domain that located at exons 1–6 and a 4 C-terminal zinc-?nger domains located at exons 7–10. One of the common genetic variant sites in WT1 gene is synonymous (Arg301) single-nucleotide polymorphism (SNP) rs16754 of WT1 (903A4G) that it is Located in Exon 7 where that is hotspot point of WT1 .most of mutation occur in exon 7, in acute leukemia.Studies have shown that this SNP independently improved overall survival (OS) and relapse-free survival (RFS) in adult AML patients.
We focused in particular on the 1 polymorphism WT1 (rs16754) and 3 polymorphisms of MEG3 (rs3087918, rs7158663, rs11160608), because mutations or epigenetic silencing could dysregulate 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. furthermore, the importance of the WT1-MEG3 axis in suppressing tumor growth could target this axis to represent a novel approach for effective AML treatment. To test our prediction we perform AML case-control study comprising 40 patients and 40 control subjects from Iran.