الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
مستخلص Acute myeloid leukemia (AML) is a genetically heterogeneous disease forming a malignant clonal proliferation of immature myeloid cells in the bone marrow, peripheral blood, and occasionally other body tissues. AML is the most common acute leukemia in adults with an overall 5-year survival rate of approximately 25%. Genetic and epigenetic profile of the leukaemic cells affects the rate of achieving remission and risk of relapse. Many of these genetic and molecular mutations in AML have prognostic implications yet; the role of epigenetics genes mutations is less clearly understood. 40 to 50% of patients have normal karyotyping. This group is considered as intermediate risk group but varies greatly in its characters and needs to be further assessed.
Ten –Eleven Translocation TET 1-3 gene family is one of the epigenetics genes. The TET protein TET 1,TET-2, TET 3 are α - ketoglutarate and Fe2+ dependent enzymes which can modify DNA methylation by converting 5- methylcystosine (5mC) into 5- hydroxymethylcystosine (5hmC). Furthermore, it can oxidize 5mC or 5hmC further and convert them to 5-formylcytosine (5fC) and/or 5-carboxylcytosine (5caC), leading to hypomethylation of genes and activation of these genes.
It was found that TET-2 gene is predominantly found in hematopoietic stem cells and has an essential role in the development and differentiation of cell lineage particularly myeloid series. TET-2 will cause hypomethylation of differentiating genes leading to differentiation of immature cells. TET-2 mutations in hematopoietic stem cells will lead to hypermethylation and silencing of genes. Similarly, mutations in the micro RNA 22 which regulates the mRNA of TET-2 gene will lead to inhibition of TET-2 expression and blocks differentiation.
The present study aimed to determining the frequency of TET-2 mutations in AML patients and to study its prognostic significance and its relation to cytogenetics.
In this study, the TET-2 gene expression by real time – PCR in 33 AML patients and 34 healthy controls of matched age and sex was measured. The median age of AML patients at presentation was 40 years with females to males ratio=1.06:1. 87.9% was