University of Khartoum

Molecular characterization of Acute Myeloid Leukemia in Sudanese patient

Molecular characterization of Acute Myeloid Leukemia in Sudanese patient

Show full item record

Title: Molecular characterization of Acute Myeloid Leukemia in Sudanese patient
Author: Salih, Setalbanat Hassan Omer
Abstract: Acute myeloid leukemia (AML) is a heterogeneous disease, therefore, various parameters are needed to classify this disease into subtypes. Mutations within the FLT3 gene, which code for the class-III-receptor kinase FLT3, ranked within the most frequent recurrent known genetic markers in acute myelocytic leukemia (AML). Internal tandem duplication (ITD) mutations in the juxtamembrane domain of FLT3 gene occur in 20 -25% of AML. NPM1mutations, the most frequent molecular alterations in acute myeloid leukemia (AML), have become important for risk stratification and treatment decisions for patients with AML in Sudan. The prognosis of AML is generally poor, this may indicate different genetic abnormalities.The aim of this study was to determine the frequency of NPM1 and FLT3-ITD single mutants in Sudanese patients with AML and correlate genetic abnormalities with hematological findings in these patients. This study explored the possibility of new SNPs in FLT-3 and NPM-1 genes in Sudanese patients with AML. Materials and methods:This was a cross sectional hospital based study carried during the period from January, 2014 to July, 2016. A total of 140 AML patients from both sexes and with different ages were included in this study. EDTA blood was collected to detect hematological parameters. DNA was extracted to detect the presence of NPM1 mutation and FLT\ITD mutation using polymerase chain reaction (PCR) and random samples was sent for sequencing by Macrogen Company in South Korea.The Data were analyzed using Bioinformatics tools. Results: A 140 patients were studied; the male to female ratio was 1:1. The age ranged between 3 years to 101 years with a mean age of 33 years, 47 were pediatric patients and 93 were adults. AML-M3 was the predominant French-American-British (FAB) subtype (29.3%) followed by M2 (19.3%), M4 (15%), M0 (12.9%), M1 (10%), M5 (6.4%), M7 (5%) and M6 (2.1%). Out of 140 patients with AML 28 patients (20%) had FLT\ITD mutation and 23 patients (16.1%) had NPM1\type A mutation. There was high correlation between two genes (p-0.002), 24% of mutant patients had double mutation.Anemia, thrombocytopenia, leukocytosis and high blast count were the characteristic features in the studied group. The presence of the FLT\ITD mutation was associated with the worse hematological abnormities.Following bioinformatics analysis two novel intronic SNPs in addition to two reported SNPs were found (rs191111314,rs397792554). Conclusions: AML-M3 was the predominant French-American-British (FAB) subtype. Gender did not affect the prevalence of AML. Frequency of FLT\ITD and NPM1 mutation was comparable to literature reports. Anemia, thrombocytopenia, leukocytosis and high blast count were predominant features. Two novel SNPs and two reported SNPs were also detected.
URI: http://khartoumspace.uofk.edu/123456789/25004


Files in this item

Files Size Format View

This item appears in the following Collection(s)

Show full item record

Share

Search DSpace


Browse

My Account