Myeloproliferative neoplasms (MPN) are a group of haematologic diseases characterized by abnormal proliferation of blood cells in the bone marrow and terminal expansion of myeloid cells in the peripheral blood. MPN are divided into 2 subgroups depending on the presence or absence of the ‘Philadelphia (Ph) chromosome’ - t(9;22)(q34.1;q11.2), i.e., the BCR-ABL1 translocation. BCR-ABL1+ MPN is chronic myeloid leukaemia (CML), which is characterized by uncontrolled production of granulocytes at different maturing stages. Given the fact that tyrosine-kinase activity of ABL is essential for malignancy transformation, 5 available tyrosine kinase inhibitors (TKIs) are recommended as first-line or second-line treatment. But among a small proportion of CML cases, resistance to TKIs develops and progression to blast phase (BP) occurs regardless of the second or third generation of TKIs.
Many studies have investigated mechanisms underlying drug resistance. Primary resistance is insensitivity and lack of response to treatment. Secondary resistance is acquired during treatment. This primary resistance of insensitivity to treatment attributes to a small subset of quiescent CML leukemia stem cells (LSCs). The persistence of quiescent CML-LSCs constitutes a reservoir that underlies the disease recurrence in case of treatment discontinuation.