POSSIBLE COEXISTENCE OF RAS ACTIVATION AND MONOSOMY-7 IN THE LEUKEMICTRANSFORMATION OF MYELODYSPLASTIC SYNDROMES

The frequency of RAS activation was studied in 48 patients with acute myeloid leukaemia (AML) or with myelodysplastic syndromes (MDS), in or der to address the question of whether patients possessing monosomy 7 or other alterations of chromosome 7 have a higher incidence of RAS ac tivation than those lacking chromosome 7 abnormalities. Samples were s creened for oncogenic point mutation by DNA amplification followed by oligonucleotide hybridization analysis at codons 12, 13 and 61 of N-RA S and codons 12 and 13 of K-RAS. Two additional samples were considere d to have activated RAS due to additional karyotypic abnormalities t(5 ;12) or loss of both copies of chromosome 17 and, hence, the neurofibr omatosis (NF1) loci. The group of chronic myelomonocytic leukaemia (CM ML) patients had activated RAS in 4/11 cases and inclusion of two CMML t patients (with monosomy 7) brings this incidence to 5/13. No change in frequency of RAS activation was seen between groups containing de n ovo AML samples with or without chromosome 7 abnormalities (1/5 and 2/ 12, respectively). However, assessment of MDS samples in the process o f, or subsequent to, leukaemic progression showed a difference between the two groups. The frequency of RAS activation in samples with monos omy 7 was 4/9 samples while none of the seven samples without chromoso me 7 changes showed RAS activation, The co-existence of RAS activation and monosomy 7 in MDS indicates that these lesions can co-operate in the multistep process of leukemogenesis.