Despite recent advancements in the therapeutic landscape of acute myeloid leukemia (AML), the prognosis of patients remains poor. Immune check point inhibitors have been investigated in hematological malignancies, including AML; however, the role of T‑cell immunoglobulin and mucin domain 3 (TIM‑3) in AML has not yet been fully elucidated. Thus, the present study aimed to investigate TIM‑3 gene expression in patients with AML and determine its associations with prognostic variables and clinical outcome. A total of 60 patients newly diagnosed with AML and 15 healthy matching individuals were recruited in the present study, and reverse transcription‑quantitative PCR analysis was performed to detect TIM‑3 expression. The results demonstrated that TIM‑3 expression was significantly upregulated in patients with AML compared with that in healthy individuals (P<0.001). In addition, patients with extramedullary disease (EMD) exhibited significantly lower median TIM‑3 expression levels compared with those without EMD (P=0.001). Furthermore, patients with high TIM‑3 expression had significantly lower complete remission rates following induction chemotherapy compared with those with low TIM‑3 expression (P=0.004). High TIM‑3 expression was significantly associated with lower overall survival rates during the 1‑year follow‑up (P=0.001). Taken together, the results of the present study suggest that TIM‑3 may act as a biomarker of a poor prognosis in patients with AML, and be used as a therapeutic target.

Necroptosis is a novel form of programmed necrotic cell death involved in various autoimmune diseases. The potential role of necroptosis in primary immune thrombocytopenia (ITP) and the possible interlink with autophagy have not been fully investigated. The gene expression of mixed lineage kinase-like domain (MLKL), receptor-interacting protein kinase 3 (RIPK3) and Beclin-1 were quantified in peripheral blood of 45 ITP patients and 20 healthy controls. Their associations with clinical, laboratory parameters and response to steroid therapy in ITP patients were evaluated. RIPK3, MLKL, and Beclin-1 were significantly upregulated in ITP patients than in healthy controls (P < 0.001). Beclin-1 mRNA levels were positively correlated with both RIPK3 and MLKL mRNA levels in ITP patients (P < 0.0001). In addition, MLKL, RIPK3, and Beclin-1 mRNA levels were inversely correlated with platelet count (r = −0.330, −0.527 and −0.608, respectively). On the hand, positive correlations between MLKL (P = 0.01), RIPK3 (P = 0.005), Beclin-1 (P = 0.002) mRNA levels and severity of bleeding in ITP patients were reported. Steroid responders (n = 18, 40%) had significantly lower MLKL, RIPK3, Beclin-1 mRNA expression levels than their levels in the non-responders (n = 27, 60%). Necroptosis may play a critical role in the pathogenesis of ITP and provide both novel therapeutic targets and promising biomarkers for the prediction of bleeding severity and treatment response in ITP patients. Additionally, this study highlighted the crosstalk between autophagy and necroptosis in ITP patients. Graphical abstract

The mechanism of the well observed hypercoagulability and high incidence of Thromboembolic Events (TE) in beta thalassemia patients has not been fully elucidated. This study aimed to evaluate evaluate the endothelial dysfunction and monocyte activation among adult Egyptian beta-thalassemic patients and assess their role in the hypercoagulability and development of TE. A total of 40 adults patients with bthalassemics and 20 healthy age and sex-matched controls were assessed for endothelial dysfunction using serum Von Willebrand Factor Antigen (VWFAg) and for monocytic activation using flow cytometric assessment of CD14 monocyte microparticles and CD11b activated monocytes. The VWF:Ag level was significantly higher among thalassemic patients (P<0.001) and was positively correlated to development of TE (P0.5) and CD11b was higher in controls (P=0.004) with no significant correlation between both and TE development (P>0.05). VWF:Ag is increased in thalassemic patients and could be used as a risk factor for thrombosis in these patients, while no identified role of activated monocytes in thrombotic tendency in such patients.

Background: Follicular lymphoma (FL) remains an incurable malignancy with heterogeneous clinical outcomes that necessitate a better understanding of disease biology. Poliovirus receptor (PVR/CD155) is markedly overexpressed in several human malignant tumors and it has a unique dual oncoimmunoregulatory role. However, the role of the soluble form of PVR (sCD155) in FL has not been fully elucidated. Methods: Soluble PVR(sCD155) were measured in the sera of 50 patients newly diagnosed with FL by sandwich enzyme-linked immunosorbent assay and compared with those of 20 healthy control participants. Moreover, we evaluated its association with the clinicopathological parameters as well as response to chemotherapy in such patients. Results: Pretreatment level of sCD155 was significantly higher in patients with FL than in control participants (P<0.001). Higher levels of sCD155 were associated with aggressive high-risk clinicopathological parameters, sCD155 levels were significantly higher in FL patients with B symptoms, advanced Ann Arbor stage III and IV, bulky disease, and high-risk cytogenetic (P-value=0.01, 0.048, 0.028 and <0.001, respectively). In addition, of the 50 patients, 24 (48%) achieved CR after 4–6 courses of chemotherapy (R-CHOP), while 26 (52%) were not in remission, and higher levels of sCD155 were associated with poor response to chemotherapy (P-value<0.001). Receiver operating characteristic curve was applied. Serum level of sCD155 higher than 4.8 ng/ml is a good predictor for poor response to chemotherapy (area under the curve: 0.857, sensitivity and specificity 88.46% and 75%, respectively). Conclusion: PVR (CD155) is a potential therapeutic target that warrants further investigations and serum sCD155 may be used as a biomarker of treatment response and for predicting poor outcome in FL.

Journal of Clinical and Diagnostic Research aims to publish findings of doctors at grass root level and post graduate students, so that all unique medical experiences are recorded in literature.