Presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of CML. In up to 95% of cases, a t(9;22) (q34;q11) translocation results in the BCR-ABL1 fusion gene (Faderl et al. 1999). This translocation results in the Philadephia chromosome. In rare CML cases lacking the traditional t(9;22) translocation, other translocations result in the creation of the BCR-ABL1 fusion gene, which sometimes involve multiple chromosomes.
ABL1 is a tyrosine kinase, and, in normal cells, it plays a role in cellular differentiation and regulation of the cell cycle. The BCR-ABL1 fusion gene creates a constitutively active tyrosine kinase, which leads to uncontrolled proliferation.

ABL1 T315I is a gatekeeper mutation that lies within the hinge region of the protein kinase domain of the Abl1 protein (PMID: 18794843). T315I has been demonstrated to occur as a secondary resistance mutation and results in increased kinase activity and transformation in the context of BCR-ABL1 in cell culture (PMID: 11423618, PMID: 18794843, PMID: 27890928), and results in reduced catalytic efficiency (kcat/km) in an in vitro assay (PMID: 30684523), but has not been fully characterized and therefore, its effect on Abl1 protein function is unknown.

Figure 1. BCR-ABL1 (E13-E2) Translocation  Sanger

Figure 2. ABL1 p.T315I  Sanger