title: The variable hematologic expression of the BCR-ABL genomic mutation and its possible determinants.
abstract: The Philadelphia (Ph) chromosome usually results from the t(9;22), which causes the physical association of the BCR1 and ABL genes and their function as a single new gene. This precise genomic mutation probably has a significant role in the development of leukemia in humans, but that leukemia may take several forms: chronic myeloid leukemia (CML), acute myeloid leukemia, acute lymphocytic leukemia, and essential thrombocythemia; CML also transforms to a lymphoid or myeloid acute phase. Two models are considered with regard to determinants of this variable hematologic expression of BCR-ABL. The first is variation in the breakpoint site of BCR1. Two breakpoint sites, M-BCR and m-BCR, are known, and their occurrence shows a nonrandom association with the different forms of leukemia. The precise position of the breakpoint within M-BCR may also be important. The second model concerns the role of other genes in determining the leukemic form shown by BCR-ABL. Results are reviewed of a patient who entered blast crisis CML and whose leukemic clones involved ten genetic loci with known leukemic associations. Many of these were probably genetic variants that allowed leukemic proliferations following the initiation of blast crisis. The multiplicity of these genes may obscure the prime determinant of blast crisis, which is unknown at the present time.
authors: Cytogenetic and Molecular Oncology Unit, Christchurch Hospital, New Zealand.
authors: P H
authors: PH
authors: Fitzgerald
authors: C M
authors: CM
authors: Morris
mesh_terms: D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D010677:Philadelphia Chromosome; D015183:Restriction Mapping; D014178:Translocation, Genetic