الفهرس 
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Abstract
Acute myeloid leukemia (AML) is heterogeneous myeloid disorder with multifactorial pathogenic mechanisms and a broad range of prognosis. AML is characterized by clonal proliferation of poorly differentiated cells of the myeloid lineage.
The pathogenesis involves recurrent genomic alterations, including somatic gene mutations and/or chromosomal abnormalities that can define biologically distinct clinical subtypes.
Comprehensive genomic profiling at the time of diagnosis can inform disease classification, risk stratification and prognosis and ultimately allow for more selective therapeutic interventions. Alterations to cellular metabolism, as well as somatic mutations of genes essential to epigenetic regulation, are implicated in the pathogenesis of several human malignancies.
Isocitrate dehydrogenases (IDHs) are homodimeric enzymes involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification.
IDH1 protein catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) to produce reduced nicotinamide adenine dinucleotide phosphate.
Diverse dioxygenases depend on sufficient levels of α-KG for multiple cellular processes, as well as for epigenetic regulation.
IDH1 enzymes are localized to the cytoplasm and peroxisomes.
Somatic mutations in IDH1 (mIDH1) genes have been described in both solid and hematological malignancies.
IDH1mutations are heterozygous, retaining one wild-type, suggestive of an oncogenic gain of function. IDH proteins are encoded by the IDH1 gene located at chromosome 2q33. Recurrent IDH1 mutations are missense variants leading to a single amino-acid substitution of arginine residues at codon 132 in exon 4 of the IDH1 gene. Additionally, a germline-synonymous single-nucleotide polymorphism (rs11554137) located in codon 105 in exon 4 of the IDH1 gene has been reported to have prognostic relevance in AML.
The aim of the present study is to detect IDH1 Mutation in adult Egyptian AML patient and find correlation between the mutation and prognosis & survival in those patients after intensive chemotherapy.
Our study included 98 subjects with newly diagnosed acute myeloid leukemia. They all presented to Ain Shams University Hospital (Hematology Unit)
All Patients included in the study were subjected to:
1) History taking and clinical examination.
2) Laboratory investigations including complete blood picture,coagulation profile, kidney, liver function tests,electrolytes and LDH.
3) Bone marrow aspirate examination at diagnosis for immunophenotyping by flow cytometry, cytogenetic studies on bone marrow aspirate and molecular study when possible.
4) Detection of IDH 1 mutation with by High Resolution Melting-PCR.
5) All patients will be followed up for their response to treatment: Follow up of the patients was done for a period of 6 months.
Our study reveals that IDH1 mutation occurs in a considerable percentage of Egyptian AML patients that shows independent bad prognostic impact on the clinical outcome. Further studies on larger CN-AML patients with more detailed molecular profile data are needed to confirm both its prevalence and prognostic impact in the presence of other gene mutations.
This will help in stratifying patients for more intensive therapy. Furthermore studies are required to clarify the exact pathogenic role that may be used to generate a targeted therapy for patients with this mutation.
Conclusion
In Conclusion, our study reveals that IDH1 mutation occurs in a considerable percentage of Egyptian AML patients that shows independent bad prognostic impact on the clinical outcome. Further studies on larger CN-AML patient cohort with more detailed molecular profile data are needed to confirm both its prevalence and prognostic impact in the presence of other gene mutations. This will help in stratifying patients for more intensive therapy. Furthermore, more studies are required to clarify the exact pathogenic role that may be used to generate a targeted therapy for patients with this mutation.