Immunological mechanisms and therapeutic advances in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is defined by the reciprocal translocation between chromosomes 9 and 22 [t(9;22)], resulting in the constitutively active BCR::ABL1 fusion oncogene in hematopoietic stem cells (HSC). CML is mostly diagnosed in older adults. However, it can also occur in children, adolescents, and young adults. Therapeutic strategies for chronic phase-CML (CML-CP) have drastically improved overall survival and disease relapse, including the development of small molecular tyrosine kinase inhibitors (TKI). However, therapeutic approaches in CML still face challenges and potential downfalls, including resistance, intolerance, persistence of leukemic cells (LCs) that risk the progression to blast phase-CML (CML-BP), and other challenges in effectiveness. Furthermore, standardized treatment by pediatric oncologists follows guidelines designed for adult CML patients and does not consider differences in host or disease biology in pediatric patients. Although some patients can achieve treatment-free remission (TFR), most patients require lifelong TKI therapy. Thus, an attractive goal in CML, particularly in children with CML, who may need several decades of TKI treatment, is to identify and target immunoregulatory pathways and restoration of immune surveillance mechanisms to promote strong immune responses and TFR success. In this review, we discuss the immunological mechanisms that contribute to the development, progression and control of CML, including supporting evidence of currently approved or investigated therapeutic approaches.