C-KIT POINT MUTATION IN PATIENTS WITH MYELOPROLIFERATIVE DISORDERS

Myeloproliferative disorders (MPD) constitute a group of hematopoietic neoplasms at the myeloid stem cell level. Myeloid stem cells and/or p rogenitor cells from MPD have been considered sensitive to hematopoiet ic growth factors, including erythropoietin, thrombopoietin and stem c ell factor (SCF). SCF is a ligand for c-kit receptor with tyrosine kin ase. We analysed the gene alteration of the c-kit extracellular domain in MPD patients by PCR-SSCP and subsequent nucleotide sequencing. The point mutation in the N-terminal part of the domain, codon 52 (Asp -- > Asn), was found in two patients with primary myelofibrosis and one w ith chronic myelogenous leukemia. We review the literature regarding t he role of SCF/c-kit system in the oncogenesis of leukemia and MPD, an d then discuss the significance of our finding in the context of growt h advantage of the mutated clones over the normal clones.