Role of Toll-Like Receptors in Myeloid Neoplasms: Focuses on the Molecular Mechanisms and Clinical Impact on Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myeloid Leukemia

Abstract

Toll-like receptors (TLRs) are essential components of the innate immune system, functioning as pattern recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In hematological malignancies, particularly myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML), TLRs influence inflammation, disease progression, and therapeutic response. This review highlights the prognostic relevance of TLR expression, the role of the MyD88 signaling pathway in clonal evolution, and the dual nature of TLR-mediated immune responses, either promoting antitumor activity or contributing to leukemogenesis. Notably, TLR dysregulation in MDS and AML is associated with poor prognosis and genomic instability, whereas in CML, TLRs contribute to a protective microenvironment via NOD-like and TNF-α pathways. Therapeutic strategies targeting TLRs, including agonists and antagonists, show promise in enhancing antitumor responses, especially when combined with agents like purine nucleoside phosphorylase inhibitors. Furthermore, genetic variations in TLR pathways may influence individual susceptibility to infection and cancer progression, reinforcing the relevance of personalized medicine. Overall, this review underscores the need for continued research into TLR modulation as a foundation for innovative therapies in hematologic cancers.