Golgi signalling proteins GOLPH3, MYO18A, PITPNC1 and RAB1B: implications in prognosis and survival outcomes of AML patients.

BACKGROUND: The role of different Golgi signalling proteins remains unexplored in the progression and spread of acute myeloid leukaemia (AML), whom all interact together in a way that facilitates proliferation and differentiation of myeloid lineage cells. OBJECTIVE: Since Golgi apparatus acts as master brain in membrane trafficking and signalling events that affect cell polarity necessary for migration, division, or differentiation; this study aims to explore the association between signalling proteins and the diagnosis, prognosis, and survival of AML patients. MATERIAL AND METHODS: This study comprised 70 newly diagnosed AML patients and 20 healthy controls to investigate the serum levels of signalling proteins; Golgi Phosphoprotein 3 (GOLPH3), Myosin 18A (MYO18A), Cytoplasmic Phosphatidylinositol Transfer Protein 1 (PITPNC1) and Ras-Associated Binding Protein 1B (RAB1B). RESULTS: AML patients showed higher serum levels of GOLPH3, MYO18A, PITPNC1 and RAB1B when compared to control (p < 0.001). A significant negative correlation was found between the patients' overall survival and GOLPH3 (p = 0.001), MYO18A (p = 0.011), PITPNC1 (p = 0.001) and RAB1B (p = 0.042). Results were confirmed by Kaplen-Meier survival analysis showing lower survival estimates in patients with higher GOLPH3 (p = 0.014), MYO18A (p = 0.047), PITPNC1 (p = 0.008) and RAB1B (p = 0.033) serum levels. CONCLUSION: GOLPH3, MYO18A, PITPNC1 and RAB1B maybe promising diagnostic and prognostic biomarkers in AML patients.

Successful Management of Severe Hyperhaemolysis with Combined Tocilizumab and Rituximab in Non-Transfusion-Dependent Thalassaemia: A Case Report.

Introduction: This is the fourth case reporting the administration of tocilizumab to control hyperhaemolysis. It was administered with rituximab to stop hyperhaemolysis refractory to frontline therapy. Hyperhaemolysis is a rare life-threatening subtype of delayed haemolytic transfusion reaction. Refractory cases pose a clinical challenge with no standard of care to date. Case Presentation: A 29-year-old lady with non-transfusion-dependent thalassaemia presented with refractory hyperhaemolysis necessitating the administration of rituximab. This was complicated with anaemic heart failure and altered sensorium exacerbated with further transfusions. A nadir haemoglobin of 2.1 g/dL was reached after the initiation of rituximab, and her condition was too critical to wait for the slow expected improvement. Hence, tocilizumab was given as a bridging therapy to block haemolysis till the delayed onset of radical treatment. Conclusion: Tocilizumab can be effectively combined with rituximab to stop hyperhaemolytic episode refractory to first-line treatment when a prompt response is needed.

Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival.

Focal adhesion kinase (FAK), human myofibrillogenesis regulator-1 (MR-1), ephrin receptor type A4 (EphA4), proto-oncogene tyrosine kinase Src (Src), and protein kinase C (PKC) are important markers in proliferation, survival, and migration in some cancers. However, the significance of each is still unclear in different malignancies, including acute myeloid leukemia (AML). Therefore, this study was conducted to investigate their serum levels in Egyptian adult de novo AML patients (n = 70) against healthy volunteers (n = 20). We managed to study the correlation between each pair and to investigate their association with diagnosis, prognosis, and survival. Serum levels were analyzed using enzyme-linked immunosorbent assay (ELISA). We found that FAK, MR-1, Src, and PKC serum levels were significantly higher in AML patients compared to control (p < 0.0001), and this was associated with significantly lower EphA4 level (p < 0.0001). Interestingly, we also observed a significant negative correlation of FAK (p = 0.027), MR-1 (p = 0.003), Src (p = 0.038), and PKC (p = 0.03) with patients' overall survival (OS) while there was a positive significant correlation between EphA4 and OS (p = 0.007). In conclusion, this study suggests that FAK, MR-1, EphA4, Src, and PKC may be used as early diagnostic and prognostic markers with high sensitivity and specificity in AML patients and thus may be incorporated into the patients' early diagnostic and prognostic panels.