Immunological Control of Chronic Myeloid Leukemia Leading to Treatment-Free Remission - Abstract
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells caused by a formation of the BCR-ABL1 chimeric gene, which encodes an aberrant tyrosine kinase with oncogenic activity. Despite the introduction of Tyrosine Kinase Inhibitors (TKIs) such as imatinib that dramatically improved the treatment of CML, CML remains incurable for the most part, and only allogeneic hematopoietic stem cell transplantation can eradicate and cure CML. This is probably
because quiescent leukemic stem cells are resistant to TKIs. However, some CML patients are able to discontinue imatinib treatment after achieving a durable deep molecular response, although they still have very low levels of residual leukemic cells. This implies that immunological control also plays a critical role in minimizing CML cells and helps maintain a complete molecular response. Indeed, recent clinical trials have suggested that the combination of imatinib with interferon-? yields stronger molecular response rates and an improved possibility of treatment-free remission. Moreover, identification of several leukemia-specific antigens is promising for the development of vaccination against CML. As a specific prognostic factor that could determine which patients can safely discontinue the treatment, natural killer cells were recently revealed to be critically important. However, cytotoxic T lymphocytes specific for CML cells could also be a good candidate for this purpose. This review summarizes the recent advances in the novel immunological aspects of CML therapy leading to treatment-free remission under immunological control of CML.