Genomically unstable cancers are dependent on specific cell cycle checkpoints to maintain viability and prevent apoptosis. The cell cycle checkpoint protein WEE1 is highly expressed in genomically unstable cancers, including diffuse large B-cell lymphoma (DLBCL). Although WEE1 inhibition effectively induces apoptosis in cancer cells, the effect of WEE1 inhibition on anti-apoptotic dependency is not well understood. We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i)...

OBJECTIVES: MYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18F-FDG PET parameters was investigated in an explorative survival analysis. METHODS: Fluorescence in situ hybridisation analysis for MYC rearrangements,...

Aim/Introduction: One of the most dire complications of hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) is the development of post-transplant lymphoproliferative disorder (PTLD). PTLD compromises a broad spectrum of disorders classified by the 2017 World Health Organization (WHO) in non-destructive, polymorphic, monomorphic and classic Hodgkin lymphoma. Distinct morphologies are associated with a more favorable clinical course and better response to initial treatment. Reduction of immunosuppression, commonly used as first-line treatment, has been associated with higher response rates in non-destructive and polymorphic PTLD, while a more aggressive...

Addition of rituximab (R) to “CHOP” (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy improved outcome for diffuse large B-cell lymphoma (DLBCL) patients. Approximately 40% of patients who receive R-CHOP still succumb to disease due to intrinsic resistance or relapse. A potential negative regulator of DLBCL treatment outcome is the CD47 “don’t eat me” immune checkpoint. To delineate the impact of CD47, we used a clinically and molecularly well-annotated cohort of 939 DLBCL patients, comprising both germinal center B-cell (GCB) and non-GCB DLBCL subtypes, treated with either CHOP or R-CHOP....

Aim/Introduction: One of the most dire complications of hematopoietic stem cell (HSCT) and solid organ transplantation (SOT) is the development of post-transplant lymphoproliferative disorder (PTLD). PTLD compromises a broad spectrum of disorders classified by the 2017 World Health Organization (WHO) in non-destructive, polymorphic, monomorphic and classic Hodgkin lymphoma. Distinct morphologies are associated with a more favorable clinical course and better response to initial treatment. Reduction of immunosuppression, commonly used as first-line treatment, has been associated with higher response rates in non-destructive and polymorphic PTLD, while a more aggressive...