Investigation of MEG3 and WT1 polymorphisms in patients with

Investigation
of MEG3 and WT1 polymorphisms in patients with acute myeloid
leukemia

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.

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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.

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