New insights into antigen specific immunotherapy for chronic myeloid leukemia

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder that is characterized by a t(9;22) translocation, which results in the expression of BCR-ABL fusion oncoproteins that are unique to the leukemic cells, necessary for oncogenesis, and potentially immunogenic [1].The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for first-line CML treatment and is increasingly used in patients with residual disease or relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite the success of imatinib and other tyrosine kinase inhibitors (TKIs), CML remains largely incurable, and this is likely due to the treatment resistance of leukemic stem cells, which are responsible for rapid disease relapse after the discontinuation of therapy. How to treat patients with CML who are resistant to BCR-ABL tyrosine kinase inhibitors is an important and urgent issue for clinical hematology. Based on experimental research exploring the imatinib resistance mechanism in CML cells, second-generation TKIs were developed. Dasatinib and nilotinib, two newer drugs with higher potency than imatinib against BCR-ABL and activity against most imatinib-resistant BCR-ABL mutations, have demonstrated superior efficacy compared with imatinib for first-line chronic-phase CML treatment in randomized phase III trials [2,3]. However, because successful treatment of a portion of patients with CML using allo-HSCT suggests the importance of immune mechanisms in eliminating leukemic cells including leukemia stem cells, TKI administration or HSCT may be combined with vaccination to cure patients with CML [4].The history of CML immunotherapetic strategies begins as early as 1975 when patients with CML received repeated intradermal BCG-cultured cell mixture injections or were vaccinated with BCG alone in a clinical immunotherapy trial, and data from cases in which intermittent busulfan therapy was used provided evidence suggesting that i