Structure of the genomic BCR and ABL loci with their respective breakpoint cluster regions (M-bcr in BCR and those indicated by vertical arrows in ABL), of the chimeric BCR-ABL mRNA transcripts (with b3a2 or b2a2 junctions), and of the p210BCR-ABLfusion protein characteristic of chronic myelogenous leukemia (CML).
Some of the important functional domains of this protein are illustrated, such as the oligomerization domain, the tyrosine 177 (Grb-2 binding site), the phospho-serine/threonine (P-S/T)-rich SH2-binding domain and the rho-GEF (dbl-like) domain on the Bcr portion; and the regulatory src-homology regions SH3 and SH2, the SH1 (kinase domain) with its main site of autophosphorylation (Y412), the nuclear localization signal (NLS), and the DNA- and actin-binding domains in the Abl moiety. Several of these domains may be targeted therapeutically with the objective of inhibiting the transforming activity of the Bcr-Abl oncoprotein.
