Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) in Innate Immunity. TLRs, NLRs, and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases

The innate immune system plays a pivotal role in the first line of host defense against infections and is equipped with patterns recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Several classes of PRRS, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) recognize distinct microbial components and directly activate immune cells. TLRs are transmembrane receptors, while NLRs and RLRs are intracellular molecules. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. The innate immune system also influences pathways involved in cancer immunosurveillance. Natural and synthetic agonists of TLRs, NLRs, or RLRs can trigger cell death in malignant cells, recruit immune cells, such as DCs, CD8+ T cells, and NK cells, into the tumor microenvironment, and are being explored as promising adjuvants in cancer immunotherapies. In this review, we provide a concise overview of TLRs, NLRs, and RLRs: their structure, functions, signaling pathways, and regulation. We also describe various ligands for these receptors and their possible application in treatment of hematopoietic diseases

Współwystępowanie nowotworów układów krwiotwórczego i chłonnego u tego samego pacjenta — dwa opisy rzadkich przypadków

The coexistence of myeloid and lymphoid malignancies in the same patient is a rare condition. In this article we describe two case reports of patients who developed these two hematological malignancies. The first patient was 25 years-old male, who developed chronic myeloid leukemia 12 months after Burkitt’s lymphoma treatment. In the second patient, 55 years-old female, plasma cell myeloma and polycythemia vera was diagnosed simultaneously. It is still unclear what mechanisms lead to development of two hematological neoplasms originating from two separate cell lineages of hematopoiesis in one patient. Larger studies to establish pathogenesis, epidemiology, prognosis but primarily diagnosis and treatment methods are required. Współwystępowanie nowotworów układów krwiotwórczego i chłonnego u tego samego pacjenta jest rzadką sytuacją. W niniejszej pracy opisano dwa przypadki pacjentów, u których rozpoznano dwa nowotwory hematologiczne. U pierwszego, 25-letniego chorego, 12 miesięcy po leczeniu chłoniaka Burkitta rozwinęła się przewlekła białaczka szpikowa. U drugiej, 55-letniej pacjentki, równocześnie rozpoznano szpiczaka plazmocytowego i czerwienicę prawdziwą. Do tej pory nie jest jasne, w jakim mechanizmie u tej samej osoby dochodzi do rozwoju chorób wywodzących się z dwóch linii komórkowych hematopoezy. Dalsze badania są niezbędne, by ustalić patogenezę, epidemiologię, rokowanie, a przede wszystkim prawidłowe algorytmy diagnozowania i leczenia pacjentów ze współwystępowaniem mieloproliferacji i limfoproliferacji.

Polymorphisms in the Genes Coding for TLRs, NLRs and RLRs Are Associated with Clinical Parameters of Patients with Acute Myeloid Leukemia

Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) are major elements of the innate immune system that recognize pathogen-associated molecular patterns. Single-nucleotide polymorphisms (SNPs) in the TLR, NLR, and RLR genes may lead to an imbalance in the production of pro- and anti-inflammatory cytokines, changes in susceptibility to infections, the development of diseases, and carcinogenesis. Acute myeloid leukemia (AML) is a bone marrow malignancy characterized by uncontrolled proliferation of transformed myeloid precursors. We retrospectively analyzed 90 AML patients. We investigated the effect of fifteen SNPs located in the genes coding for RLR1 (rs9695310, rs10738889, rs10813831), NOD1 (rs2075820, rs6958571), NOD2 (rs2066845, rs2066847, rs2066844), TLR3 (rs5743305, rs3775296, 3775291), TLR4 (rs4986791, rs4986790), and TLR9 (rs187084, rs5743836). We observed that TLR4 rs4986791, TLR9 rs5743836, and NOD2 rs2066847 were associated with CRP levels, while RLR-1 rs10738889 was associated with LDH level. Furthermore, we found TLR3 rs5743305 AA to be more common in patients with infections. We also found TLR9 rs187084 C to be associated with more favorable risk, and RLR-1 rs9695310 GG with higher age at diagnosis. In conclusion, the current study showed that SNPs in the genes encoding TLRs, NLRs, and RLRs may be potential biomarkers in patients with AML