Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy

Abstract

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidants, oncolytic virus, engineered exosomes, and natural products obtained from marine organisms that could pave the way for new therapeutic approaches for CML patients.

Keywords: Non-BCR-ABL targeted drugs; antioxidants; chronic myeloid leukemia; exosomes; marine organisms; oncolytic therapy; quiescent leukemia stem cells; tyrosine kinase inhibitors.

Figure 1

Current status of TKI therapy for CML. (A) Most approved drugs recognize the binding site for ATP in BCR-ABL, as: Imatinib, Dasatinib, Nilotinib, Bosutinib, and Ponatinib. Asciminib binds to the myristoyl pocket of the BCR-ABL kinase. The new molecules of third and fourth generation TKIs including: Olverembatinib (HQP1351), Vodobatinib (K0706) and PF-114. (B) Omacetaxine is an approved inhibitor that blocks protein synthesis.