A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia.
The transforming genes of oncogenic retroviruses are homologous to a group of evolutionary conserved cellular onc genes. The human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuL V) was recently shown to be located on chromosome 9. The long arm of this chromosome is involved in a specific translocation with chromosome 22, the Philadelphia translocation (Ph1), t(9; 22) (q34, q11), which occurs in patients with chronic myelocytic leukaemia (CML)3-5. Here we investigate whether the c-abl gene is included in this translocation. Using c-abl and v-abl hybridization probes on blots of somatic cell hybrids, positive hybridization is found when the 22q- (the Philadelphia chromosome), and not the 9q+ derivative of the translocation, is present in the cell hybrids. From this we conclude that in CML, c-abl sequences are translocated from chromosome 9 to chromosome 22q-. This finding is a direct demonstration of a reciprocal exchange between the two chromosomes and suggests a role for the c-abl gene in the generation of CML.
D002904:Chromosomes, Human, 21-22 and Y; D002906:Chromosomes, Human, 6-12 and X; D004273:DNA, Neoplasm / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D009857:Oncogenes; D014178:Translocation, Genetic
D004273:DNA, Neoplasm