MOLECULAR DEFECTS ASSOCIATED WITH THE ACUTE-PHASE CML

Parts of the Bcr/Abl hybrid transcript supposed to be important for it s transforming ability were sequenced in a series of CML blast crises, in order to evaluate the possible presence of alterations responsible for the disease transition from the chronic to the acute phase. In ad dition, the N- and Ki-ras as well as the p53 involvement was investiga ted by exploring their structure and expression in the same patients. We used traditional types of molecular analysis including Southern and Northern blot, together with methods that allow a rapid detection of point mutations and microdeletions, such as SSCP, single strand confor mation polymorphism and direct sequencing. The results obtained may be summarized as follows: no alterations were found in the parts of the Bcr/Abl transcripts investigated in the present study (SH2, SH3 and th e region surrounding codon 832); p53 alterations were observed in 5% a nd N- and Ki-RAS mutations in 5% of the cases examined. These molecula r defects are therefore responsible for the clinical progression of th e Ph1-positive CML only in a minority of cases.