The cytokine network in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous malignancy of the blood and bone marrow, characterized by clonal expansion of myeloid stem and progenitor cells and rapid disease progression. Chemotherapy has been the first-line treatment for AML for more than 30 years. Application of recent high-throughput next-generation sequencing technologies has revealed significant molecular heterogeneity to AML, which in turn has motivated efforts to develop new, targeted therapies. However, due to the high complexity of this disease, including multiple driver mutations and the coexistence of multiple competing tumorigenic clones, the successful incorporation of these new agents into clinical practice remains challenging. These continuing difficulties call for the identification of innovative therapeutic approaches that are effective for a larger cohort of AML patients. Recent studies suggest that chronic immune stimulation and aberrant cytokine signaling act as triggers for AML initiation and progression, facets of the disease which might be exploited as promising targets in AML treatment. However, despite the greater appreciation of cytokine profiles in AML, the exact functions of cytokines in AML pathogenesis are not fully understood. Therefore, unravelling the molecular basis of the complex cytokine networks in AML is a prerequisite to develop new therapeutic alternatives based on targeting cytokines and their receptors.

Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal

“…Argentine Stop Trial (AST), to date, is the largest clinical trial in Latin America of chronic phase (CP)-CML patients who stopped across all types of tyrosine kinase inhibitors (TKIs) (Additional file 1 : Supp Materials and Methods). Cytokine profiling has been suggested to be valuable in identifying predictive markers in other myeloid malignancies [ 1 ]; here, we measured plasma cytokine levels in 46 patients discontinuing TKIs with the aim of identifying predictive plasma biomarkers for TFR. Patients baseline characteristics and treatment information are shown in Additional file 2 : Table S1.…”

Y‐box binding protein 1 in small extracellular vesicles reduces mesenchymal stem cell differentiation to osteoblasts—implications for acute myeloid leukaemia

“…In acute myeloid leukaemia (AML), it is well known that abnormal secretion of pro‐inflammatory cytokines remodels the bone marrow microenvironment (BMM) in favour of AML blast survival, AML progression, and treatment resistance (Kupsa et al., 2012 ; Luciano et al., 2022 ). However, few recent studies have demonstrated that small extracellular vesicles (sEVs) released by AML cells transform the BMM into a leukaemia‐permissive microenvironment.…”

Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia

“…Additionally, the immune-modulatory properties of AML-MSCs, demonstrated by their ability to induce regulatory T cells, suggest their involvement in shaping the immunosuppressive microenvironment supporting leukemic cells [ 68 ]. The interaction between AML blasts and MSCs results in the release of cytokines and chemokines, contributing to the formation of a leukemic niche [ 69 ].…”