[Transforming gene in the preleukemic state].

Abstract

The presence of a transforming gene in the DNA of bone marrow cells from patients with myelodysplastic syndrome (MDS) was studied using an in vivo selection assay in which NIH 3T3 cells transfected with human DNA were injected into nude mice in order to observe the growth of the tumor. The transforming gene was present in 12 out of 18 cases. The Alu sequence was demonstrated in the tumor grown after injection of transfected NIH 3T3 cells from 10 patients. Among these 10 Alu sequences, the human N-ras oncogene was present in 3 cases. Analysis of nucleotide sequences of the exons of human N-ras oncogenes cloned from the tumors revealed a single point mutation of the codon encoding the 13th amino acid of exon 1 from guanine to cytosine in all 3 cases of MDS. A one-year follow-up study of these MDS cases showed that in the patients positive for the transforming gene, the disease state progressed from PARA, PASA to RAEB or from RAEB to acute leukemia in 6 out of 7 cases, while in the 6 negative patients, no change was observed in their disease states. It was considered that the mutation of the N-ras gene at the 13th amino acid codon of exon 1 was fairly specific to MDS and that presence of the transforming gene may be used for predicting the progress of the disease.