Detection of KIT and FLT3 mutations in acute myeloid leukemia with different subtypes.
BACKGROUND
Mutations in KIT and fms-like tyrosine kinase 3 genes lead to uncontrolled proliferation of leukemic cells with a poor prognosis. Since, data concerning the incidence and associations with patients characteristics vary amongst different studies, the aim of the present study is to identify and quantify the frequency of mutations in Iranian patients suffering from acute myeloid leukemia.


METHODS
Internal tandem duplication and D835 mutations in the fms-like tyrosine kinase 3 gene of acute myeloid leukemia patients were studied through polymerase chain reaction and polymerase chain reaction-RFLP analysis. Amplified products for a point mutation in D816 for KIT have also been identified through the polymerase chain reaction-RFLP technique. The mutations in exon 8 of KIT were detected by using the PCR and the Conformational Sensitive Gel Electrophoresis techniques, and amplified products have been confirmed by sequencing techniques.


RESULTS
Internal tandem duplication and D835 mutations in the fms-like tyrosine kinase 3 gene occurred in 18% and 6% of AML patients, respectively. Frequencies of mutation were 1.4% and 4.7% in exon 8 and D816 of the KIT gene in acute myeloid leukemia patients. These results were substantially different for various subclasses of French-American-British classification.


CONCLUSIONS
This study revealed that approximately 30% of acute myeloid leukemia patients have either KIT or fms-like tyrosine kinase 3 genetic mutations. The presence of fms-like tyrosine kinase 3 was significantly associated with M3 morphology and mutations of KIT were significantly associated with M2 and M4 subtypes.
Zaker
Farhad
F
Oncopathology Research Center, Cellular and Molecular Research Center, Iran University of Medical Sciences, Hemmat Freeway, Tehran, Iran. farhadz20@yahoo.co.uk
Mohammadzadeh
Mohammad
M
Mohammadi
Mohammad
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3