Targeting DNA Repair, Cell Cycle, and Tumor Microenvironment in B Cell Lymphoma

The DNA double-strand break (DSB) is the most cytotoxic lesion and compromises genome stability. In an attempt to efficiently repair DSBs, cells activate ATM kinase, which orchestrates the DNA damage response (DDR) by activating cell cycle checkpoints and initiating DSB repair pathways. In physiological B cell development, however, programmed DSBs are generated as intermediates for effective immune responses and the maintenance of genomic integrity. Disturbances of these pathways are at the heart of B cell lymphomagenesis. Here, we review the role of DNA repair and cell cycle control on B cell development and lymphomagenesis. In addition, we highlight the intricate relationship between the DDR and the tumor microenvironment (TME). Lastly, we provide a clinical perspective by highlighting treatment possibilities of defective DDR signaling and the TME in mantle cell lymphoma, which serves as a blueprint for B cell lymphomas

Books in Arabic Script

The chapter approaches the book in Arabic script as the indispensable means for the transmission of knowledge across Eurasia and Africa, within cultures and across cultural boundaries, since the seventh century ad. The state of research can be divided into manuscript and print studies, but there is not yet a history of the book in Arabic script that captures its plurilinear development for over fourteen hundred years. The chapter explores the conceptual and practical challenges that impede the integration of the book in Arabic script into book history at large and includes an extensive reference list that reflects its diversity. The final published version was slightly updated, and includes seven illustrations of six Qurans from the holdings of Columbia University Libraries, four manuscripts and two printed versions. Moreover, the illustrations are images of historical artifacts which are in the public domain - despite Wiley's copyright claim

Novel therapeutic approaches in relapsed or refractory Hodgkin lymphoma

Background While classical Hodgkin lymphoma (HL) is curable in most cases with risk-adapted first-line therapy, the treatment of patients with relapsed or primary refractory (r/r) HL in particular remains a challenge. Methods This review article discusses the currently available data on the safety and efficacy of newer therapeutic approaches for r/r HL from a practice-oriented perspective. Results In patients suitable for intensified therapy, durable remission can be achieved in approximately 50% of cases with polychemotherapy-based salvage followed by high-dose chemotherapy with autologous stem cell transplantation (ASCT). With the approval of targeted agents, even multiply relapsed, refractory, elderly, or multimorbid patients now have multiple treatment options. In addition to the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV), the two anti-PD1 antibodies nivolumab and pembrolizumab are increasingly being used here as immune checkpoint inhibitors. The anti-PD1 antibodies are also used in earlier lines of therapy, e.g., significantly longer progression-free survival (PFS), was achieved with pembrolizumab in an international phase III trial compared to BV with comparable response rates. The therapeutic landscape of r/r HL is rapidly changing and additional promising targeted agents such as the antibody-drug conjugate camidanlumab tesirine, different checkpoint inhibitors, and anti-CD30 CAR T cells are currently being tested in trials. Conclusions Rational use of available therapeutic approaches is expected to improve the prognosis of patients with multiple r/r HL