BCR-ABL1 fusion proteins have multiple isoforms. The 210 kDa isoform exists in over 90–95% of CML patients, one-third of ALL patients and 1–2% of AML patients, while the 190 kDa isoform is found in two-thirds of ALL patients and 3% of atypical CML patients. Disease progression often leads to drug resistance related to BCR-ABL1 mutations. Patients with T315I point mutation develop resistance to imatinib and all second-generation TKIs, and detection of this mutation provides a basis for selecting third-generation TKI therapies.

 Regular high-quality molecular monitoring minimizes the risk of disease progression and maximizes the likelihood of achieving treatment-free remission (TFR) to optimize therapeutic outcomes.

Early detection of elevated BCR-ABL1 levels or failure to reach predefined remission targets may necessitate mutation analysis. Patients experiencing treatment failure should be switched to more effective TKI treatment.

Sustained deep molecular response (DMR) correlates with successful TFR. Optimizing treatment strategies to maximize the chance of achieving DMR (3 years for MR4.0 patients, 2 years for MR4.5 patients) is an increasingly important therapeutic target for CML.