Targeted and Immune-Based Therapies for Acute Myeloid Leukemia: Inflammatory Signaling and Multiple Post-Translational Modifications

Abstract

Acute myeloid leukemia (AML) is an aggressive cancer of cells derived from the myeloid lineage. The disease is characterized by an arrest in cellular differentiation and subsequent accumulation of abnormal myeloid precursor cells in the bone marrow. The standard treatment is combination chemotherapy comprising cytarabine plus an anthracycline. However, long-term survival outcomes for adult AML patients remain unchanged the past 40 years. Without postremission treatment, most patients relapse and die of the disease. Cellular therapy in the form of allogenic hematopoietic stem cell transplantation (HSCT) is the most successful postremission treatment for younger adults with AML. However, the risk for transplant-related mortality is high due to increased frequency of infections and graft-versushost disease [1]. Moreover, intensive chemotherapy and HSCT is often not eligible for patients above 70 years of age. Novel treatments such as immunotherapy and/or drugs that target molecular aberrations that perturb signaling could represent safe and beneficial alternatives or adjuvants to enhance efficacy of the current chemotherapy regimen for AML. The purpose of this focused issue is to highlight new advances in targeted therapies for AML, including anti-inflammatory and immunomodulatory agents such as checkpoints inhibitors, chemokine receptor antagonists and antibody-directed drug delivery to the leukemic stem cells by using immunoliposomes. Potential therapeutic modulation of aberrant posttranslational modifications, inflammatory signaling and G protein-coupled receptors (GPCRs) signaling will be presented.