A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia

Abstract

The Philadelphia (Ph) chromosome breakpoints in chronic myelocytic leukaemia are clustered on chromosome 22 band q11 in a 5.8-kilobase (kb) region designated bcr. The c-abl protooncogene is translocated from chromosome 9 band q34 into bcr and the biochemical consequence of this molecular rearrangement is the production of an abnormal fusion protein bcr-abl p210 with enhanced protein-tyrosine kinase activity compared to the normal p145 c-abl protein. The Ph chromosome translocation is also seen in some acute lymphoblastic leukaemias with B-cell precursor phenotypes some of which have bcr rearrangement (bcr +) and some do not (bcr -). We present evidence that the Ph +, bcr - leukaemias are associated with a novel p190 abl kinase. We propose that acute lymphoblastic leukaemias that are bcr +, p210 + are probably lymphoid blast crises following a clinically silent chronic phase of chronic myelocytic leukaemia arising in multipotential stem cells whereas bcr -, p190 + cases are de novo acute lymphoblastic leukaemias arising in more restricted precursors.