Expression of c-abl in Philadelphia-positive acute myelogenous leukemia.
The identical cytogenetic marker, t(9;22)(q34;q11) (Philadelphia [Ph] translocation), is found in approximately 90%, 20%, and 2% of adult patients with chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML), respectively. In CML, the molecular events resulting from the Ph translocation include a break within the bcr locus on chromosome 22, transfer of the c-abl protooncogene from chromosome 9 to 22, and formation of an aberrant 210-kD bcr-abl fusion protein (p210bcr-abl). Recently, the absence of bcr rearrangement and expression of a distinct aberrant 190-kd abl protein (p190c-abl) has been described in Ph-positive ALL, with the suggestion that the two abl variants may be pathogenetically associated with myeloid v lymphoid leukemogenesis. Here we report that the genomic configuration and translation product of Ph-positive AML can be similar to that of Ph-positive ALL: the break at 22q11 may occur outside the 5.8 kb bcr region and result in expression of a 190-kD abl protein lacking these bcr sequences. Phosphokinase enzymatic activity, a fundamental property of p210bcr-abl, was also associated with AML-derived p190c-abl. Our current observations indicate that p190c-abl can be found in cells of lymphoid or myeloid lineage and is therefore unlikely to play a specific role in the development of lymphoid leukemias. Formation of p190c-abl instead of p210bcr-abl appears to be a characteristic of the acute rather than the chronic Ph-positive leukemic state.
Kurzrock
R
R
Department of Clinical Immunology, M.D. Anderson Hospital and Tumor Institute at Houston, TX 77030.
Shtalrid
M
M
Talpaz
M
M
Kloetzer
W S
WS
Gutterman
J U
JU
D002460:Cell Line; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid; D007951:Leukemia, Myeloid / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D010677:Philadelphia Chromosome; D011519:Proto-Oncogenes; D014158:Transcription, Genetic