**3. Chronic myeloid leukemia (CML)**

CML is a myeloproliferative disorder characterized by the presence of the BCR-ABL oncogene fusion protein, resulting from reciprocal translocation between chromosomes 9 and 22 [t(9;22)], commonly designed by Philadelphia chromosome (Ph chromosome) (Ref). As a result, Bcr-Abl tyrosine kinase becomes constitutively activated and triggers apoptosis resistance and other biological alterations responsible for CML pathogenesis. With the introduction of tyrosine kinase inhibitors (TKIs), significant benefits for CML patients are currently achieved. Nilotinib, dasatinib, and imatinib are the commonly TKIs small molecules used in the clinic for the treatment of CML. These inhibitors are designed to block the adenosine triphosphate-binding site of the Bcr-Abl tyrosine kinase and inhibit the activation of downstream effector proteins, responsible for CML exacerbations.

The success of TKI therapy is associated with the reduction of BCR-ABL1 transcript levels in the CML patients. Current guidelines refer to major molecular response (MMR) for the BCR-ABL1 level not exceeding 0.1% or deep molecular response (DMR) for the BCR-ABL1 level not exceeding 0.01%. DMR can be achieved in almost 50% of CML patients who stopped TKI treatments. However, important questions remain regarding the mechanisms leading to CML remission and lack of relapse. Addressing such questions will help identify biomarkers that could predict which patient could discontinue TKI therapy without relapse and also determine the long-term success of the treatment.
