Extranodal NK/T-cell lymphoma (ENKL) is an aggressive hematological malignancy associated with Epstein–Barr virus (EBV) infection. It is often resistant to conventional chemotherapy and has a poor prognosis. Icaritin, a compound derived from Chinese herbal medicine, Herba Epimedii, has been reported to exert antitumor effects on a variety of cancer cell lines. In the present study, we investigated the cytotoxic effects of Icaritin on the two EBV-positive ENKL cell lines SNK-10 and SNT-8, along with the underlying molecular mechanisms. ENKL cell lines SNK-10 and SNT-8 were exposed to different concentrations of Icaritin for the indicated time. Treated cells were analyzed for cell proliferation, cell cycle, and cell apoptosis. Phosphorylation of Stat3 and Akt proteins in signaling pathways and the EBV-encoded LMP1 proteins were measured by Western blot. Expression of EBV genes was assessed by Real-Time PCR. Our results showed that Icaritin dose-dependently inhibits ENKL cell proliferation and induces apoptosis and cell cycle arrest at G2/M phase. Additionally, Icaritin upregulates Bax, downregulates Bcl-2 and pBad, and activates caspase-3 and caspase-9. The anti-proliferative and pro-apoptotic effects of Icaritin are likely mediated by inhibition of Stat3 and Akt pathways through LMP1 downregulation. Importantly, Icaritin induces EBV lytic gene expression in ENKL cells, and the combination of Icaritin and the antiviral drug ganciclovir (GCV) is more effective in inducing ENKL cells apoptosis than Icaritin or GCV alone. These findings indicate that EBV-targeted approaches may have significant therapeutic potential for ENKL treatment.
Rationale: Pure erythroid leukemia (PEL) is a rare and highly aggressive subtype of acute myeloid leukemia. Herein, a rare case of de novo PEL with rapid progression harboring EZH2 and TP53 frameshift mutations was reported. Patient concerns: A 57-year-old male presented with a 3-week history of pancytopenia and peripheral blasts (9%). He also had a 6-day history of hematemesis. Diagnoses: The case was diagnosed as PEL. Bone marrow examination, immunophenotype, gene mutation analysis, and karyotyping confirmed the diagnosis of PEL. Interventions: Early in his illness, the patient received acid suppression therapy, gastric protection, hemostatic treatment, and transfusions of red blood cell suspension and platelet concentrates at a local hospital. He was later transferred to our hospital, where the diagnosis of PEL was made, and induction chemotherapy was initiated. Outcomes: Following chemotherapy, the patient developed granulocytopenia, severe anemia, and thrombocytopenia. He required multiple transfusions of apheresis platelets and red blood cell suspensions for symptomatic relief. However, due to financial concerns, the patient discontinued treatment and passed away 20 days after starting therapy. Lessons: Due to the unclear pathogenesis of PEL and the lack of targeted therapeutic drugs, the prognosis is inferior. Further research into the signaling pathways regulated by the identified mutations and their potential as therapeutic targets is essential to improve the prognosis of this aggressive form of leukemia.
High-dose chemotherapy with autologous stem cell transplantation (ASCT) is a key consolidative therapy for primary central nervous system lymphoma (PCNSL). However, the optimal regimen for mobilizing haematopoietic stem cells remains undefined in this population, leading to unpredictable failure rates and suboptimal cell yields. We retrospectively analysed data from 142 patients with histologically confirmed PCNSL who underwent stem-cell mobilisation before ASCT. Three mobilisation strategies were compared: high-dose cytarabine (HD-Ara-C)–based mobilisation (n = 64), plerixafor plus G-CSF (n = 60), and cyclophosphamide (CTX, n = 18). Mobilisation success, CD34⁺ cell yield, toxicity, and predictors of collection outcomes were evaluated. Patients in the HD-Ara-C–based mobilisation group achieved a 100% success rate, significantly outperforming CTX (77.8%) and steady-state mobilisation (98.3%) while delivering a markedly superior median CD34⁺ cell yield (20 × 10⁶/kg vs. 12.7 and 10 × 10⁶/kg, p < 0.001). Notably, 79.7% of patients in the HD-Ara-C–based mobilisation group were classified as “very good” mobilisers,with all “poor” mobilisers confined to the other groups. Crucially, we identified and validated the first-day peripheral blood CD34⁺ cell count as a powerful predictor of collection outcome. A threshold of > 31 cells/µL predicted successful collection (> 2 × 10⁶/kg) with an AUC value of 0.94 (98.6% specificity, 78.6% sensitivity). Higher thresholds predicted optimal and high-yield collections. Although grade 4 thrombocytopenia was more common with HD-Ara-C, it was manageable with supportive care. HD-Ara-C–based mobilisation is a highly effective strategy for PCNSL, ensuring universal success and maximizing CD34⁺ cell yields. The first-day CD34⁺ cell count provides a robust, real-time tool for guiding apheresis. HD-Ara-C–based mobilisation should be considered the preferred regimen for fit patients, with steady-state mobilisation as an alternative for selected cases.