Burkitt Lymphoma

Together, our data indicate that ZDHHC11 promotes BL cell growth at least in part by stimulating expression of MEF2B, which promoted BL cell survival through both BCL6-dependent and independent pathways. Our work highlighted the importance of the MEF2B-BCL6 axis, which strongly supports BL growth and identified ZDHHC11 as a novel regulator of this axis.

P1/2, N=20, Recruiting, New York Medical College | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Aug 2024 --> Aug 2026

Therefore, we upgraded the treatment plan to R-CHOP chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), and achieved a complete remission (CR)...We observe that the combination of HD-MTX and intrathecal chemotherapy exhibits remarkable efficacy in managing post-transplant CNS-PTLD that is resistant to conventional R-CHOP chemotherapy. CAR-T therapy emerges as a potential option for patients suffering from relapsed or refractory CNS-PTLD.

Here, we identify EBV latent membrane protein 1 (LMP1), a key viral oncogene necessary for B cell immortalization and which mimics aspects of CD40 signaling, drives resistance to ferroptosis induction by erastin, a small molecule that blocks cystine uptake...PFKFB4 was also necessary for LMP1-mediated Burkitt B cell ferroptosis resistance. Collectively, these results identify PFKFB4 as a key host cell EBV metabolism remodeling target critical for infected B cell redox defense.

EBV-activated JunB played an obligatory role in repression of the G1/S phase inhibitor CDKN2C /p18 INK4c in LCLs but not Burkitt B cells. These findings establish an LMP1-JunB-p18 INK4c axis as essential for EBV-driven lymphoblastoid B cell proliferation, suggest JunB-mediated cross-talk between Epstein-Barr nuclear antigens and LMP1, and highlight JunB as a potential therapeutic target for EBV-associated lymphoproliferative disorders.

P1, N=16, Completed, Calibr, a division of Scripps Research | N=36 --> 16 | Trial completion date: Aug 2036 --> Oct 2025 | Trial primary completion date: Aug 2036 --> Oct 2025 | Enrolling by invitation --> Completed

We therefore characterized the impact of pan-HDAC inhibitor, panobinostat, and class I HDAC inhibitor, nanatinostat, on the growth, survival, and lytic reactivation of four EBV-positive cell lines: P3HR1-ZHT BL, Jijoye BL, IBL-1 immunoblastic lymphoma, and de novo infection derived lymphoblastoid cell lines (LCL). Functional validation through a Cas9-RNP approach revealed that the CD137 receptor is indeed involved in preventing successful lytic reactivation. These data have important implications for how we approach oncolytic therapies for EBV-associated malignancies.

P2, N=24, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Given persistent cholestasis and bleeding risk, the patient underwent Roux-en-Y choledochojejunostomy for biliary decompression, followed by initiation of rituximab-cyclophosphamide-vincristine-doxorubicin-high-dose methotrexate/rituximab-ifosfamide-etoposide-high-dose cytarabine (R-CODOX-M/R-IVAC) with central nervous system prophylaxis...Ampullary BL should be considered in pediatric patients with obstructive jaundice and upper gastrointestinal bleeding. Surgical biliary decompression can stabilize cholestasis and facilitate timely multi-agent chemotherapy.

EBNA1 upregulates the expression of miR-127-5p through demethylation, promoting the proliferation and glycolytic metabolism of EBV+ BL cells, and inhibiting cells apoptosis.

The human de-ubiquitinase enzyme USP17 is likely to be responsible for this effect, as upregulation of USP17 is induced by EBV lytic proteins. This study provides new insight into how EBV manipulates epigenetic mechanisms to regulate latency and lytic reactivation and reveals novel potential therapeutic targets.

These findings contribute to a better understanding of the genetic factors influencing BL susceptibility and support the need for further functional and large-scale studies to elucidate the mechanistic role of MMP-2 and MMP-9 polymorphisms in BL pathogenesis.