CHANGES IN ONCOGENE EXPRESSION IMPLICATED IN EVOLUTION OF CHRONIC GRANULOCYTIC-LEUKEMIA FROM ITS CHRONIC PHASE TO ACCELERATION

Expression of nine oncogenes was investigated in cell samples from fif teen patients with Philadelphia chromosome (Ph)-positive chronic granu locytic leukemia (CGL) both at diagnosis and at the onset of accelerat ed phase (AP) of the disease. The bcr-abl fusion gene, the H-ras gene and the c-myb gene were universally expressed. In comparison with the chronic phase (CP) of the disease, an increase in the levels of bcr-ab l-, c-myb- and H-ras-related transcripts was found in three, two and t hree AP samples, respectively. Elevation of the bcr-abl-related messag e was associated with duplication of the Ph chromosome and amplificati on of the bcr-abl fusion gene in one AP sample. No CP samples were pos itive for c-myc or c-sis expression. On the contrary, c-myc and c-sis were expressed in three and four AP samples, respectively. The presenc e of c-myc-related transcript was associated with trisomy 8 with or wi thout amplification of the c-myc oncogene in leukemia cells of two pat ients with CGL in AP. No changes of oncogene expression were found in four AP samples. However, we observed deletions of chromosome 13 and 1 7 or i(17q) in three of them, suggesting that tumor suppressor gene al terations may also be responsible for the development of AP of CGL. Ou r data indicate that heterogeneous alterations in oncogenes and tumor suppressor genes accompany the evolution of CGL-CP to the AP of the di sease.