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.