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

Background: Primary refractory acute myeloid leukemia (AML) represents a continuing obstacle in clinical management. The Runt-related transcription factor 1 (RUNX1) gene is a relatively uncommon mutational target in AML cases. Aim: to investigate the role of RUNX1 mutation in newly diagnosed refractory AML patients receiving first-line induction chemotherapy.Methods: Our research involved 50 newly diagnosed Egyptian AML patients; As a control group, 20 newly diagnosed AML patients who received the conventional first induction chemotherapy with complete remission (CR) and 30 newly diagnosed AML patients who received the same conventional first induction chemotherapy protocols but did not respond to the treatment.Results: 13.3% of the examined cases group had RUNXI mutations found, compared to 5% of the control group, RUNXI mutation was found statistically significant with cases group (P=0.01) and RUNX1 mutation and OS were significantly correlated (P=0.05). Conclusion: RUNX1 mutation have a role in resistance to treatment and prognosis in AML. Therefore, measurement of RUNX1 level provides a new strategy to more aggressive treatments for primary refractory AML cases.

Background: Osteoblasts, the cells that make up bone, produce and secrete fibroblast growth factor 23 (FGF23). People with chronic renal disease had a higher-than-normal levels of FGF23 in their blood. Objective: The goal of this study was to examine FGF23's possible predictive function for renal impairment (RI) in patients with multiple myeloma (MM). Patients and Methods: Intact FGF23 serum levels were measured in four groups of patients: 1st Group: 20 MM patients with RI either on dialysis or not; 2nd Group: 20 MM patients without RI; 3rd Group: 30 healthy individuals; 4th Group: 10 RI patients without MM. Results In this study, we found that both MM patients with and without RI had elevated levels of FGF23 (mean=158.50 and 94.75, respectively) than in healthy individuals (mean=25.17). The difference in results between the MM and healthy individual groups was highly significant (p < 0.01). Patients with MM and RI have greater serum iFGF23 levels compared to those with MM and no RI (p < 0.05). Significant direct link exists between iFGF23 and creatinine (p < 0.01), (r=0.689). There is a strong inverse correlation between eGFR and iFGF23 in the serum (p < 0.01). Conclusion: FGF23 levels increase significantly in MM with RI patients and are higher in MM patients with RI than those without RI. Renal impairment in MM may be diagnosed and predicted with the help of FGF23.