• Breakpoint cluster region-Abelson murine leukemia
• Chronic myeloid leukemia
• Diagnosis
• Immunotherapy
• Philadelphia chromosome
• Tyrosine kinase inhibitors

• Antigen presentation
• BCR-ABL
• CTL Response
• Cytoplasmic transduction peptide
• DC Vaccine

• CML
• Chronic myeloid leukemia
• immunogenicity
• interferon with TKI
• leukemia-associated antigens
• tumor antigen-specific immunotherapy
• vaccines

Chronic myeloid leukemia (CML) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in CML patients at diagnosis, prior to TKI therapy. TKIs such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (DMR, BCR-ABL1 ≤ 0.01%) in CML patients. As a result, the more recent goal of therapy in CML treatment is to induce a durable DMR as a prelude to successful treatment-free remission (TFR), which occurs in approximately half of all CML patients who cease TKI therapy. The lack of overt relapse in such patients has been attributed to immunological control of CML. In this review, we discuss an immunological timeline to successful TFR, focusing on the immunology of CML during TKI treatment; an initial period of immune suppression, limiting antitumor immune effector responses in newly diagnosed CML patients, linked to an expansion of immature myeloid-derived suppressor cells and regulatory T cells and aberrant expression of immune checkpoint signaling pathways, including programmed death-1/programmed death ligand-1. Commencement of TKI treatment is associated with immune system re-activation and restoration of effector-mediated [natural killer (NK) cell and T cell] immune surveillance in CML patients, albeit with differing frequencies in concert with differing levels of molecular response achieved on TKI. DMR is associated with maximal restoration of immune recovery in CML patients on TKI. Current data suggest a net balance between both the effector and suppressor arms of the immune system, at a minimum involving mature, cytotoxic CD56^dim NK cells may be important in mediating TFR success. However, a major goal remains in CML to identify the most effective pathways to target to maximize an advantageous immune response and promote TFR success.

• chronic myeloid leukemia
• deep molecular response
• immune surveillance
• immunology
• treatment-free remission

• BCR-ABL1
• CML stem cells
• chronic myeloid leukemia
• drug resistance
• oncogene addiction
• tyrosine kinase inhibitor

• Algorithms
• Child
• Diagnosis, Computer-Assisted
• Humans
• Lung Diseases/diagnosis
• Respiratory Sounds
• Signal-To-Noise Ratio

• R01 AG036424 NIA NIH HHS
• 1R01AG036424 NIA NIH HHS

• CML
• LAAs
• bcr-abl
• cancer vaccines
• immunology
• immunotherapy
• tyrosine kinase inhibitors

• BCR-ABL1
• Chronic myeloid leukemia
• Hematopoietic stem cell transplant
• Tyrosine kinase inhibitor

• Algorithms
• Cancer Vaccines
• Computer Simulation
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology
• Models, Biological
• Monte Carlo Method
• Vaccination

Chronic myeloid leukemia (CML) is a stem cell disease in which BCR/ABL plays an important role as an oncoprotein and a molecular and immunogenic target. Despite the success of targeted therapy using tyrosine kinase inhibitors (TKIs), CML remains largely incurable, most likely due to the treatment resistance of leukemic stem cells. Several immunotherapies have been developed for CML in different stages and relapse after allogeneic stem cell transplantation. In the this review, several specific immunotherapeutic approaches for CML, including vaccination and adoptive cellular immunotherapy, are discussed along with results from clinical trials, and the value of such immunotherapies in the era of imatinib and leukemia-associated antigens (LAAs), which are capable of inducing specific T cell responses and are appropriate target structures for the immunological targeting of CML cells, are also summarized.