Amina Wahid, BS Zoology, 2015-2019, Supervised by Dr. Afia Muhammad Akram
Screening of C-kit exon 8 mutations and their prognostic significance in acute myeloid leukemia (AML) patients from Pakistan
/ Amina Wahid
- Lahore : Division of Science & Technology, University of Education, 2019
- xv, 63 p. CD
Acute myeloid leukemia (AML) is a disorder of blood and is a heterogeneous disease. Cytogenetic abnormalities, translocations and gene mutations are key events in the development of acute myeloid leukemia. C-kit gene is one of the proto-oncogenes, which is expressed in germ cells, mast cells and hematopoietic stem cells, and code for c-kit receptor (transmembrane receptor tyrosine kinase). Objective of this study was to determine the occurrence of mutations in c-kit exon 8 among Pakistani population with acute myeloid leukemia, and their association with clinical and hematological parameters. Blood samples were taken from newly diagnosed AML patients (n=31) and a control. Samples from control and patients with acute myeloid leukemia were analyzed for c-kit exon 8 mutations by using Polymerase chain reaction (PCR) and Sanger sequencing techniques. Population variation in c-kit exon 8 at nucleotide position 1368 in healthy Pakistani population was identified at beginning of the analysis and was not considered as mutation in further analysis. Fifteen out of 31 AML patients were found to have c-kit exon 8 mutations at the time of diagnosis. Mutation resulting in change of Adenine (A) to Guanine (G) was observed in 60% of mutant AML patients at position 1279 (Arg420Gly). Insertions of Guanine (G) at different positions (1280, 1282, 1288, 1289, 1291, 1292, 1294, 1295, 1297 and 1393) and Thymine (T) at position 1287 and 1325 are also observed in ckit exon 8 in AML patients which result in frame shift of subsequent translation sequence. C-kit exon 8 mutations were significantly associated with FAB type (p=0.029), Spleen size (p=0.038) and red blood cell count (p=0.007). These findings can help to find out prognostics significance and to estimate overall survival of AML patients with c-kit exon 8 mutations.