Possible co-existence of RAS activation and monosomy 7 in the leukaemic transformation of myelodysplastic syndromes.
The frequency of RAS activation was studied in 48 patients with acute myeloid leukaemia (AML) or with myelodysplastic syndromes (MDS), in order to address the question of whether patients possessing monosomy 7 or other alterations of chromosome 7 have a higher incidence of RAS activation than those lacking chromosome 7 abnormalities. Samples were screened for oncogenic point mutation by DNA amplification followed by oligonucleotide hybridization analysis at codons 12, 13 and 61 of N-RAS and codons 12 and 13 of K-RAS. Two additional samples were considered to have activated RAS due to additional karyotypic abnormalities t(5;12) or loss of both copies of chromosome 17 and hence, the neurofibromatosis (NF1) loci. The group of chronic myelomonocytic leukaemia (CMML) patients had activated RAS in 4/11 cases and inclusion of two CMMLt patients (with monosomy 7) brings this incidence to 5/13. No change in frequency of RAS activation was seen between groups containing de novo AML samples with or without chromosome 7 abnormalities (1/5 and 2/12, respectively). However, assessment of MDS samples in the process of, or subsequent to, leukaemic progression showed a difference between the two groups. The frequency of RAS activation in samples with monosomy 7 was 4/9 samples while none of the seven samples without chromosome 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.
Stephenson
J
J
Department of Haematological Medicine, Kings College School of Medicine and Dentistry, London, UK.
Lizhen
H
H
Mufti
G J
GJ
D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D005786:Gene Expression Regulation; D011905:Genes, ras; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D017354:Point Mutation