Epstein-Barr Virus Promotes Tumorigenicity and Worsens Hodgkin Lymphoma Prognosis by Activating JAK/STAT and NF-κB Signaling Pathways.

Background: Epstein-Barr virus (EBV) is detected in 40% of patients with Hodgkin lymphoma (HL). During latency, EBV induces epigenetic alterations to the host genome and decreases the expression of pro-apoptotic proteins. The present study aimed to evaluate the expression levels of mRNA molecules and the end product of proteins for the JAK/STAT and NF-κB pathways, and their association with clinicopathological and prognostic parameters in patients with EBV-positive and -negative classical Hodgkin lymphoma (CHL). Methods: A prospective cohort study was conducted from 2017 to 2022 at the Faculty of Medicine, Zagazig University Hospital (Zagazig, Egypt). Biopsy samples of 64 patients with CHL were divided into EBV-positive and EBV-negative groups. The expression levels of mRNA molecules (JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, COX-2) and the end product of proteins (PD-L1, Bcl-xL, COX-2) were determined and compared with clinicopathological and prognostic parameters. Data were analyzed using the Chi square test and Kaplan-Meier estimate. Results: EBV-positive CHL patients were significantly associated with positive expression of mRNAs molecules (P<0.001) and the end product of proteins (P<0.001) for the JAK/STAT and NF-κB pathways, B-symptoms (P=0.022), extra-nodal involvement (P=0.017), and advanced stage of CHL (P=0.018). These patients were more susceptible to cancer progression, higher incidence of relapse (P=0.008), poor disease-free survival rate (P=0.013), poor overall survival rate (P=0.028), and higher mortality rate (P=0.015). Conclusion: Through the activation of JAK/STAT and NF-κB signaling pathways, EBV-positive CHL is associated with poor clinicopathological parameters, higher incidence of disease progression, relapse, and poor overall survival. A preprint of this manuscript is available on research square (doi: 10.21203/rs.3.rs-1857436/v1).

Relation between mutations in the 5' UTR of ANKRD26 gene and inherited thrombocytopenia with predisposition to myeloid malignancies. An Egyptian study.

Inherited thrombocytopenias are a heterogeneous group of diseases characterized by a reduced number of platelets and a bleeding tendency that ranges from very mild to life threatening especially in surgery. Mutations in the 5' untranslated region (UTR) of Ankirin repeat domain 26 (ANKRD26) are responsible for autosomal-dominant form of thrombocytopenia, that is known as ANKRD26-related thrombocytopenia (ANKRD26 RT), characterized by a moderate thrombocytopenia with mild propensity to bleeding and predisposition to hematological malignancies including AML and MDS. We included 90 unrelated patients with inherited thrombocytopenia. In addition, we investigated 45 patients with ITP. Peripheral blood and bone marrow samples were collected and examined and molecular detection of mutations in the 5︡ UTR of ANKRD26 gene was performed for all the patients. Also, screening of the mutation and development of myeloid malignancies in the extended series of the affected subjects was done. ANKRD26 mutations were identified in 10% of the patients with inherited thrombocytopenia. The most common types were c.128 G > A and c.127A>T, while no mutations were found in the ITP group. In those affected, the median number of platelets was 69 x109/L (43-106) with normal MPV in most of the patients (9.4-11.6). There was a statistically significant increase in the unexpected high frequency of myeloid malignancies in the extended series of the mutated subjects compared with the ITP group-extended series (P < .001). So, we can conclude that ANKRD26 RT is associated with increased risk for developing myeloid malignancies and ANKRD26 mutations can represent a valuable tool for making therapeutic decisions.