Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients

Aref, Salah; Elmaksoud, AL Shaimaa Mansoura Abd; El-Aziz, Sherin Abd; Mabed, Mohamed; Ayed, Mohamed Ben

doi:10.31557/apjcp.2020.21.11.3177

Cited by 8 publications

(19 citation statements)

References 21 publications

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“…Other studies have investigated the possible importance of TLR4 genetic polymorphisms and the clinical course for acute leukemia patients receiving intensive and potentially curative acute leukemia treatment: One study investigated eight single nucleotide polymorphisms (SNPs) in 194 children with acute lymphoblastic leukemia (ALL), and the four SNPs rs10759931, rs11536889, rs1927911 and rs6478317 were associated with increased risk of treatment-induced cytopenia [ 87 ]. The TLR4 Asp299Gly polymorphism seems to influence the risk of sepsis after AML therapy [ 88 ]. Another study also described an association between this SNP and the risk of both sepsis and pneumonia; the same associations were described for the Thr399Ile TLR4 polymorphism whereas the TLR2 polymorphism Arg753Gln was only associated with pneumonia [ 89 ].…”

Section: Tlr4 Mediated Immunoregulation In Aml; the Importance Of Gen...mentioning

confidence: 99%

“…On the other hand, another study described an association between invasive aspergillosis and the Asp299Gly/Thr399Ile variants in the donor or recipient after allogeneic stem cell transplantation [ 91 ]. The TLR4 Asp299Gly polymorphism was associated with relapse risk in one previous study [ 88 ], and a study of European children with ALL suggested an association between TLR6 SNPs and risk of leukemia [ 92 ]. …”

Section: Tlr4 Mediated Immunoregulation In Aml; the Importance Of Gen...mentioning

confidence: 99%

“…The TLR4 Asp299Gly polymorphism seems to influence the risk of sepsis after AML therapy [ 88 ]. Another study also described an association between this SNP and the risk of both sepsis and pneumonia; the same associations were described for the Thr399Ile TLR4 polymorphism whereas the TLR2 polymorphism Arg753Gln was only associated with pneumonia [ 89 ].…”

Section: Tlr4 Mediated Immunoregulation In Aml; the Importance Of Gen...mentioning

confidence: 99%

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Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia

2022

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Toll-like receptor 4 (TLR4) is a pattern-recognizing receptor that can bind exogenous and endogenous ligands. It is expressed by acute myeloid leukemia (AML) cells, several bone marrow stromal cells, and nonleukemic cells involved in inflammation. TLR4 can bind a wide range of endogenous ligands that are present in the bone marrow microenvironment. Furthermore, the TLR4-expressing nonleukemic bone marrow cells include various mesenchymal cells, endothelial cells, differentiated myeloid cells, and inflammatory/immunocompetent cells. Osteoblasts are important stem cell supporting cells localized to the stem cell niches, and they support the proliferation and survival of primary AML cells. These supporting effects are mediated by the bidirectional crosstalk between AML cells and supportive osteoblasts through the local cytokine network. Finally, TLR4 is also important for the defense against complicating infections in neutropenic patients, and it seems to be involved in the regulation of inflammatory and immunological reactions in patients treated with allogeneic stem cell transplantation. Thus, TLR4 has direct effects on primary AML cells, and it has indirect effects on the leukemic cells through modulation of their supporting neighboring bone marrow stromal cells (i.e., modulation of stem cell niches, regulation of angiogenesis). Furthermore, in allotransplant recipients TLR4 can modulate inflammatory and potentially antileukemic immune reactivity. The use of TLR4 targeting as an antileukemic treatment will therefore depend both on the biology of the AML cells, the biological context of the AML cells, aging effects reflected both in the AML and the stromal cells and the additional antileukemic treatment combined with HSP90 inhibition.

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Section: Tlr4 Mediated Immunoregulation In Aml; the Importance Of Gen...mentioning

confidence: 99%

Section: Tlr4 Mediated Immunoregulation In Aml; the Importance Of Gen...mentioning

confidence: 99%

Section: Tlr4 Mediated Immunoregulation In Aml; the Importance Of Gen...mentioning

confidence: 99%

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Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia

2022

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“…In light of this evidence, it seems advantageous to continue research on TLR4 and its inhibitor, as it may be a good strategy for the treatment of TLR4-expressing AML in the future. Aref et al investigated the impact of TLR2 and TLR4 polymorphisms on the survival of patients with AML and their susceptibility to severe infections [ 293 ]. They demonstrated that, in AML patients with TLR2 Arg753Gln with an AG genotype and an A allele, TLR4 Asp299Gly with a CT genotype and a C allele, and TLR4 Thr399Ile with an AG genotype and an A allele, pneumonia and sepsis were more frequent than in patients with other genotypes and alleles.…”

Section: Future Perspectives In the Treatment Of All Or Amlmentioning

confidence: 99%

“…This study showed that, in these patients, TLR polymorphism translates into both their risk of infection and survival. However, more research is needed on this point [ 293 ].…”

Section: Future Perspectives In the Treatment Of All Or Amlmentioning

confidence: 99%

Insights into Modern Therapeutic Approaches in Pediatric Acute Leukemias

Panuciak

Margas

MAKOWSKA

et al. 2022

Cells

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Pediatric cancers predominantly constitute lymphomas and leukemias. Recently, our knowledge and awareness about genetic diversities, and their consequences in these diseases, have greatly expanded. Modern solutions are focused on mobilizing and impacting a patient’s immune system. Strategies to stimulate the immune system, to prime an antitumor response, are of intense interest. Amid those types of therapies are chimeric antigen receptor T (CAR-T) cells, bispecific antibodies, and antibody–drug conjugates (ADC), which have already been approved in the treatment of acute lymphoblastic leukemia (ALL)/acute myeloid leukemia (AML). In addition, immune checkpoint inhibitors (ICIs), the pattern recognition receptors (PRRs), i.e., NOD-like receptors (NLRs), Toll-like receptors (TLRs), and several kinds of therapy antibodies are well on their way to showing significant benefits for patients with these diseases. This review summarizes the current knowledge of modern methods used in selected pediatric malignancies and presents therapies that may hold promise for the future.

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Association of Toll-like receptors polymorphisms with the risk of acute lymphoblastic leukemia in the Brazilian Amazon

Xabregas

Hanna

Souza

et al. 2022

Sci Rep

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Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children in childhood. Single-nucleotide polymorphism (SNPs) in key molecules of the immune system, such as Toll-like receptors (TLRs) and CD14 molecules, are associated with the development of several diseases. However, their role in ALL is unknown. A case–control study was performed with 152 ALL patients and 187 healthy individuals to investigate the role of SNPs in TLRs and the CD14 gene in ALL. In this study, TLR6 C > T rs5743810 [OR: 3.20, 95% CI: 1.11–9.17, p = 0.003) and TLR9 C > T rs187084 (OR: 2.29, 95% CI: 1.23–4.26, p = 0.000) seems to be a risk for development of ALL. In addition, the TLR1 T > G rs5743618 and TLR6 C > T rs5743810 polymorphisms with protection against death (OR: 0.17, 95% IC: 0.04–0.79, p = 0.008; OR: 0.48, 95% IC: 0.24–0.94, p = 0.031, respectively). Our results show that SNPs in TLRs genes may be involved in the pathogenesis of ALL and may influence clinical prognosis; however, further studies are necessary to elucidate the role of TLR1, TLR4, TLR5, TLR6, TLR9 and CD14 polymorphisms in this disease.

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Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients

Abstract: About eleven human TLRs have been identified up till now and each of them participates in a specific intracellular signaling pathway. TLRs 1, 2, 4, 5 and 6 are typical for bacterial products, TLRs 3, 7 and 8 are characteristic for viral infection and TLR9 is associated

Cited by 8 publications

References 21 publications

Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia

Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia

Insights into Modern Therapeutic Approaches in Pediatric Acute Leukemias

Association of Toll-like receptors polymorphisms with the risk of acute lymphoblastic leukemia in the Brazilian Amazon

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