EXPRESSION OF THE C-KIT PROTOONCOGENE IN MYELOPROLIFERATIVE DISORDERSAND MYELODYSPLASTIC SYNDROMES

The c-kit proto-oncogene is the receptor gene for the stem cell growth factor. Little is known about the distribution and role of this gene product in malignant hematopoiesis. We analysed here the expression of c-kit in myeloproliferative disorders (MPDs), including chronic myelo genous leukemia (CML), essential thrombocythemia (ET), polycythemia ve ra (PV), and idiopathic myelofibrosis (IMF) and in the myelodysplastic syndromes (MDS). The c-kit expression of peripheral blood mononuclear cells was measured both at the messenger RNA level using Northern ana lysis, the RNA dot blot technique with densitometric quantification, t he sensitive reverse transcription polymerase chain reaction, and at t he protein level using immunofluorescence with monoclonal antibodies. There was a statistically significant increase in c-kit messenger leve ls in CML, ET, PV, IMF, and MDS as compared with controls (healthy vol unteers). The percentage of c-kit protein expressing cells was also hi gher than in the controls in these disorders. There was a significant correlation of the c-kit protein expression with the CD34 antigen of t he cells. Expression correlated with the phase of the disease, being h ighest in the blast crisis of CML and in the RAEB/RAEBt phases of MDS. The data suggest that increased amounts of circulating stem/progenito r cells with c-kit receptor are found in MPDs and MDS. It is possible that elevated c-kit expression could maintain the affected clone in MP Ds and MDS.