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Fig. 2 | Molecular Cancer

Fig. 2

From: Chronic myeloid leukemia: the paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy

Fig. 2

Genomic breakpoints in the BCR and ABL1 genes and resulting transcript types and proteins. a Translocation breakpoints in BCR most frequently fall in intron 13 or 14 (M-BCR) or in intron 1 (m-BCR), or in intron 19 (μ-BCR). In ABL1, the breakpoints are intronic as well, and most frequently fall in a large region comprised between exons 1b and 2. Exon 1a and 1b are mutually exclusive and are incorporated in the mature ABL1 mRNA as a result of alternative splicing. However, neither of the two is retained in BCR-ABL1 mRNA. b The most common fusion transcripts resulting from the translocation include e13a2 and e14a2, resulting from the M-BCR, both translated into the p210BCR-ABL1 isoform (typical of CML and of some cases of Ph + ALL); e1a2, resulting from the m-BCR and translated into the p190BCR-ABL1 isoform (typical of the majority of Ph + ALL); e19a2, resulting from the μ-BCR and translated into the p230BCR-ABL1 isoform (typical of a subset of CML once called chronic neutrophilic leukemias). c Domain organization of BCR, ABL1 and BCR-ABL1 proteins. BCR is a 160 kDa protein with a coiled-coil (CC) oligomerization domain, a domain thought to mediate binding to Src-homology 2 (SH2)-domain-containing proteins, a serine/threonine kinase domain, a region with homology to Rho guanine-nucleotide-exchange factor (Rho-GEF), a region thought to facilitate calcium-dependent lipid binding (CaLB) and a region showing homology to Rac GTPase activating protein (Rac-GAP). ABL1 is a 145 kDa protein that contains an N-cap (that in isoform 1b undergoes myristoylation, a post translation modification that attaches the fourteen-carbon saturated fatty acid myristate to the amino-terminal glycine of the protein), the tandem SH3, SH2 and SH1 (tyrosine-kinase) domains, four proline-rich SH3 binding sites (PXXP), three nuclear localization signals (NLSs), one nuclear exporting signal (NES), a DNA-binding domain, and an actin-binding domain. In all BCR-ABL1 protein isoforms, the CC domain of BCR is included, the myristoylated N cap is lost, and the ABL1 kinase domain is retained. National Center for Biotechnology Information (NCBI) accession numbers: ABL1 gene, NG_012034.1; BCR gene, NG_009244.1

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