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

Abstract

The Philadelphia (Ph) chromosome breakpoints in chronic myelocytic leukaemia are clustered on chromosome 22 band qll in a 5.8-kilobase (kb) region designated bcr¹. 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 proteinbcr–abl p210 with enhanced protein-tyrosine kinase activity^2,3 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^4,5 some of which have bcr rearrangement (bcr⁺) and some do not (bcr^-)^6,7. 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.