Burkitt Lymphoma

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.

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.

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2027

P=N/A, N=1000, Recruiting, French Africa Pediatric Oncology Group | Trial completion date: Dec 2028 --> Dec 2030 | Trial primary completion date: Dec 2027 --> Dec 2028

P2, N=60, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Jan 2028 --> Mar 2029 | Trial primary completion date: Feb 2026 --> Apr 2027

We also provide a comprehensive overview of the findings convincingly demonstrating that subtyping of BL into EBV-positive and EBV-negative better describes the biological heterogeneity of this lymphoma entity than the historical subtyping into endemic, sporadic, and immunodeficiency-associated. As the distinction of BL from other B-cell lymphomas is important for providing optimal oncological care, we also discuss the differential diagnosis and how this lymphoma can be distinguished from other aggressive B-cell lymphomas.

Results from this study highlight the importance of assessing inter-patient variation in NK cell profiles in conjunction with ADCC sensitivity and EBV type within tumor cells when evaluating clinical outcomes for NK-mediated immunotherapies. EBV type dictates NK cytotoxicity: EBV-T1 BL cells require rituximab for NK killing, while EBV-T2 BL cells are eliminated without antibody assistance, highlighting target-specific immune response to EBV-associated cancers.

P=N/A, N=50, Recruiting, Children's Hospital of Philadelphia | Trial completion date: Jun 2027 --> Feb 2028 | Trial primary completion date: Jun 2026 --> Feb 2027

The combination of KPT-8602 and IFN-γ can activate the pan-apoptotic pathway by upregulating ZBP1, thereby effectively inhibiting the growth of PCNSL. This study presented a promising new combination treatment strategy for PCNSL.

Our study provides a comprehensive assessment of the spectrum of MYC, BCL2, and BCL6 rearrangements based on FISH and IHC analysis results.