Absence of point mutations in a functionally important part of the extracellular domain of the c-kit proto-oncogene in a series of patients with acute myeloid leukemia (AML).
The proto-oncogenes c-fms and c-kit belong to a family of growth factor receptors possessing protein kinase activity. It has been shown that transfection of a c-fms gene carrying a point mutation at codon 301, leads to a ligand-independent transformation of mouse NIH3T3 cells. In human acute myeloid leukemia (AML), point mutations at codon 301 of the c-fms gene have been observed implying an important role in the transformation process. The possibility of a point mutation of the c-kit proto-oncogene was investigated. We sequenced a segment of the c-kit proto-oncogene coding for a part of the extracellular domain. This segment was 40.7% homologous to the c-fms region encompassing codon 301. c-DNA was prepared from peripheral blood or bone marrow cells from 25 patients with AML, from four patients with myelodysplastic syndrome (MDS) and from three human myeloid cell lines. The region of interest was amplified with two rounds of polymerase chain reactions (PCR) with nested primers and directly sequenced. No point mutations were found in the investigated samples. Thus, point mutations in this segment of the c-kit gene do not seem to play an important role in the transformation process of human acute leukemia.
Arland
M
M
Department of Oncology/Hematology, University Hospital Eppendorf, Hamburg, Germany.
Fiedler
W
W
Samalecos
A
A
Hossfeld
D K
DK
D000208:Acute Disease; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D017422:Sequence Analysis, DNA
D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas