Toll-Like Receptor 4, 2, and Interleukin 1 Receptor Associated Kinase4: Possible Diagnostic Biomarkers in Myelodysplastic Syndrome Patients

Abstract

Background: Myelodysplastic syndrome (MDS) is a clonal hematologic disorder that requires the integration of morphologic, cytogenetic, hematologic, and clinical findings for a successful diagnosis. Trying to find ancillary tests such as biomarkers improve the diagnosis process. Several studies showed that a disordered immune system is associated with MDS. The chronic activated innate immune system, particularly the Toll-like receptors (TLRs) pathway could be involved in the induction of the inflammation.

Materials and methods: In the present study, we investigated the expression of TLR2, TLR4, and IRAK4 in bone marrow (BM) of MDS patients, the leukemia group, and the healthy group. For this purpose, we assessed the expression of TLR2, TLR4, and IRAK4 by real time-PCR.

Results: In line with new findings, we demonstrated that the expression of TLR2, TLR4, and IRAK4 significantly increased in MDS BM compared with the healthy group. Moreover, IRAK4 expression raised significantly in MDS patients compared with other studied hematologic neoplasms. Also, the expression levels of TLR2 and TLR4 significantly increased in MDS in comparison to some studied non-MDS malignancies (P ˂ 0.05). Receiver operating characteristics (ROC) analysis and area under the curve (AUC) suggested that the expression of TLR2, TLR4, and IRAK4 (AUC = 0.702, AUC = 0.75, and AUC = 0.682, respectively) had acceptable diagnostic values to identify MDS from the other understudied leukemias.

Conclusion: Overall, the expression of TLR2, TLR4, and IRAK4 could be potential biomarkers for discriminating MDS from some hematologic disorders.

Keywords: IRAK4; TLR2; TLR4; myelodysplastic syndrome.

Figure 1

Comparison of TLR2, TLR42, and IRAK4 gene expressions in BM cells of MDS patients and health controls by the quantitative reverse transcriptase-polymerase chain reaction. The healthy controls included five persons with normal bone marrow and no history of cancer. Error bars correspond to mean ± SEM; P ˂ 0.05 is significant. MDS: myelodysplastic syndrome

Figure 2

Quantification of TLR2 (a), TLR4 (b), and IRAK4 (c) in BM cells of MDS and non-MDS disorders by the quantitative reverse transcriptase-polymerase chain reaction. Error bars correspond to mean ± SEM; P ˂ 0.05 is significant. MDS: myelodysplastic syndrome, AML: Acute myeloid leukemia, ALL: Acute Lymphoblastic leukemia, CLL: Chronic Lymphoblastic leukemia, MM: Multiple myeloma

Figure 3

Receiver operating curve (ROC) analysis of TLR2, TLR4, and IRAK4 gene expression to determine diagnostic accuracy in differentiation of MDS patients with other hematologic disorders. AUC: area under the curve