Introduction: Acute myeloid leukemia (AML) is characterized by clonal expansion of malignant myeloid blast cells in the bone marrow with impaired normal hematopoiesis. AML is a hematopoietic disorder characterized by multiple cytogenetic and molecular abnormalities and accounts for 25% of childhood leukemia diagnoses. The prognosis of childhood AML remains poor, with a recurrence rate of approximately 30%. Therefore, to increase the efficiency of treatment, new treatment approaches are necessary. A common feature in AML is an altered epigenetic pattern resulting from somatic mutations in epigenetic regulators or specific translocations that interfere with the normal epigenetic program. Several important molecular markers such as IDH1/2, FLT3, NPM1 and CEBPA mutations have been identified in the prognostic classification of AML with normal cytogenetics (CN-AML), Mutations in these genes have been shown to have clinically significant prognostic value. Isocitrate dehydrogenases (IDHs) are a group of enzymes that convert isocitrate to α-ketoglutarate (α-KG) in two steps in the Krebs cycle (TCA). Driving mutations in IDH1 and IDH2 have been observed in several tumors including glioma, AML, myeloproliferative neoplasm, chondrosarcoma, lymphoma, melanoma and thyroid cancer. As a result of these mutations, an oncometabolite called hydroxyglutarate is produced, which plays a role in tumorigenesis. The purpose of this study is to investigate the mutation rate of IDH1/2 genes in AML patients of Shariati Hospital in Tehran and the relationship of these mutations with other genetic mutations of FLT3 and NPM1.
Methods: At first, DNA of AML patients was extracted from peripheral blood (PB) and bone marrow (BM) samples. Then, using the HRM technique, the mutation rate of IDH1/2 genes in these patients was investigated and compared with the DNA sample purified from the blood of a healthy person (Wild Type).
Results: In the conducted study, the presence of IDH1 and IDH2 mutations was investigated by HRM molecular method. Among the 88 sample cases, 15 cases (17%) of mutated IDH1 and 16 cases (18%) of mutated IDH2 were observed. In this study, statistically significant relationship between IDH1/2 mutation and FLT3 mutation and platelet count (Plt) was not observed (P value>0.05). However, a significant relationship between IDH1 mutation and NPM1 mutation, overall survival (OS) and white blood cell (WBC) count was observed (P value<0.05), also in this study, IDH2 mutation did not show a significant relationship with overall survival (OS) and WBC count (P value>0.05).
Conclusion: In general, in this study, only NPM1 mutation, WBC count and overall survival rate (OS) were significantly correlated with IDH1 mutation, but no significant correlation was observed between any of the mentioned variables with IDH2 mutation.