Molecular Structure of Philadelphia Chromosome Positive Leukaemias

Abstract

The Philadelphia chromosome was the first specifıc karyotype abnormality associated with a particular neoplastic disease in humans. The Ph translocation generats a hybrid gene consisting of 5' exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. The molecular consequence of this translocation is the transcription of chimaeric m RNA and transcribed in a novel 210 kd protein (p 210) in CML, an p 190 kd protein in ALL which retain the tyrosine-kinase activity derived from the ABL sequences. Although the breakpoints on chromoseme 9 can occur over a 200 KB range the breakpoint on chromosome 22 are usually clusteret within a 5 KB sequence designated the breakpoint cluster region. in some Philadelphia positive acute lymphoblastic leukaemias, however, the break in the bcr gene has been shown to lie further 5' such that only the first exon ofbcr is includled in the chimaeric m RNA.