A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia.
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.
D000293:Adolescent; D000328:Adult; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010677:Philadelphia Chromosome; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis*
D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D004262:DNA Restriction Enzymes