Acute myelogenous leukemia (AML) is a heterogeneous group of disease characterized by uncontrolled proliferation of myeloid progenitor cells. It is clear that TET2 polymorphisms are common among Egyptian AML patients and larger scale studies are needed to iinvestigate the role of this in both modulating treatment and prognostic impact of the disease. TET2 mutations are established poor prognostic molecular risk factors yet TET2 polymorphism status are not thoroughly studied. Role of miRNA22 and its impact on TET2 expression needs to be further studied to improve risk stratification of AML.
The aim of this study is to evaluate the incidence of the TET2 single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) and its correlation to miRNA22 gene expression in Egyptian Adult Acute Myeloid Leukemia patients.
Cases were selected from Alexandria Main University Hospital Internal Medicine Department (Hematology Unit) from March 2017-December 2017; 52 patients diagnosed as AML and 30 healthy subjects matched for age and sex to determine SNPs genotype frequency among patients. DNA extraction by Invitrogen purelink genomic DNA minikit (Cat No. k1820-01, Lot No 1510617) and real time PCR for TET2 SNP polymorphism using Taqman primers and probes of TET2 polymorphism (rs2454206, rs34402524, rs61744960) using an ABI Prism GeneAmp 7500 using peripheral or bone marrow blood. Micro RNA 22 Taqman quantitative Assay using real time PCR (Thermal Fisher Biosystems Taqman miRNA22 Cat. no. 4427975) and control miRNA was U6. Micro RNA extraction was done using Qiagen extraction kits (Cat No./ID: 217004). Written Informed consent was taken from every patient and approval of the Ethical committee (IRB No. 00008699, FWA No.00015712) was provided.
35 AML patients (14 females, 21 males) had mean age of 43.42 ± 14.0yrs are the subject of the study. SNP RS 34402524 ranged from heterozygous (23/52 46%) to homozygous (27/52 54%) in AML group but was mainly homozygous (24/30 80%) among the control group (p>0.05). As for RS 6843141, most AML patients had wild pattern (31/52 62%) and control group were homozygous (20/30 60%) (p < 0.0001). RS 2454206, and RS 61744960 showed no statistical significance between cases and controls (p > 0.05). miRNA22 were under-expressed among AML most patients. This was of statistical significance compared to controls p < 0.0001. As for miRNA 22 and TET2 polymorphism, there was no statistical significance between the status of SNPs and miRNA22 expression p > 0.05.
miRNA22 is markedly underexpressed in AML patients and may participate in hypermethylation and leukomogenesis. Confirmation of this finding could open a new therapeutic approach in AML and even in bone marrow transplant candidates.