Explore the vast range of titles available.

Background Relapse is a major cause of treatment failure in high-risk acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cell immunotherapy may enhance graft-versus-leukemia (GvL) effects without increasing graft-versus-host disease (GvHD). This study assessed the safety and feasibility of early post-HSCT prophylactic infusions of third-party NK cells in high-risk AML. Methods In a single-arm, non-randomized trial, 11 high-risk AML patients received two doses of ex vivo expanded third-party NK cells (5 × 10⁶ cells/kg) on days 6 and 12 post-HSCT. Endpoints included safety (CTCAE v5.0), relapse incidence, overall survival (OS), and disease-free survival (DFS). NK cell products were assessed for purity (≥ 80% CD56⁺CD3⁻), cytotoxicity (K562 assay), and expansion. Results NK cell infusion was well tolerated, with no grade 3 or higher infusion-related toxicities. Acute GvHD (Grade 1–2) occurred in 36.4% (4/11); chronic GvHD in 27.3% (3/11). CMV reactivation occurred in 45.5% (5/11) and was managed preemptively. At a median 256-day follow-up (54–514), Relapse occurred in 27.3% (3/11; median: 111 days). Survival was significantly better in patients in CR1/CR2 at HSCT (83.3%) compared to those not in remission (20%; p  = 0.02). Conclusion Early prophylactic NK cell infusions post-HSCT are safe and feasible. Although relapse incidence remains substantial, outcomes appear improved versus historical data. Future randomized trials must confirm clinical benefits and refine timing/dosing strategies.

Background Leukemia, a type of blood cell cancer, is categorized by the type of white blood cells affected (lymphocytes or myeloid cells) and disease progression (acute or chronic). In 2020, it ranked 15th among the most diagnosed cancers and 11th in cancer-related deaths globally, with 474,519 new cases and 311,594 deaths (GLOBOCAN2020). Research into leukemia’s development mechanisms may lead to new treatments. Ubiquitin-specific proteases (USPs), a family of deubiquitinating enzymes, play critical roles in various biological processes, with both tumor-suppressive and oncogenic functions, though a comprehensive understanding is still needed. Aim This systematic review aimed to provide a comprehensive review of how Ubiquitin-specific proteases are involved in pathogenesis of different types of leukemia. Methods We systematically searched the MEDLINE (via PubMed), Scopus, and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) to identify relevant studies focusing on the role of USPs in leukemia. Data from selected articles were extracted, synthesized, and organized to present a coherent overview of the subject matter. Results The review highlights the crucial roles of USPs in chromosomal aberrations, cell proliferation, differentiation, apoptosis, cell cycle regulation, DNA repair, and drug resistance. USP activity significantly impacts leukemia progression, inhibition, and chemotherapy sensitivity, suggesting personalized diagnostic and therapeutic approaches. Ubiquitin-specific proteases also regulate gene expression, protein stability, complex formation, histone deubiquitination, and protein repositioning in specific leukemia cell types. Conclusion The diagnostic, prognostic, and therapeutic implications associated with ubiquitin-specific proteases (USPs) hold significant promise and the potential to transform leukemia management, ultimately improving patient outcomes.

Ubiquitin-specific peptidases (USPs), also known as deubiquitinating enzymes (DUBs), play a crucial role in maintaining cellular homeostasis by selectively removing ubiquitin molecules from targeted proteins. This process affects protein stability, subcellular localization, and activity, thereby influencing processes such as DNA repair, cell cycle regulation, and apoptosis. Abnormal USP activities have been linked to various diseases, including cancer. Emerging evidence in lymphoma studies highlights the significance of USPs in controlling signaling pathways related to cancer initiation and progression and presents them as potential therapeutic targets. This study aimed to elucidate the multifaceted roles of USPs in lymphoma. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published in English up to May 2023 were retrieved from PubMed, Web of Science, and Scopus. The inclusion criteria focused on studies investigating the role of USPs in lymphoma cancer, involving human subjects or relevant lymphoma cell lines, exploring molecular mechanisms and signaling pathways, and assessing diagnostic or prognostic value. After the selection process, 23 studies were selected for analysis. USPs were found to affect various aspects of lymphoma development and progression. Specific USPs were identified with roles in cell-cycle regulation, apoptosis modulation, drug resistance, DNA repair, and influence of key oncogenic pathways, such as B cell receptor (BCR) signaling. This systematic review underscores the emerging role of USPs in lymphoma and their potential as therapeutic targets. Inhibitors of USPs, such as USP14 inhibitors, show promise in overcoming drug resistance. The dynamic interplay between USPs and lymphoma biology presents an exciting opportunity for future research and the development of more effective treatments for patients with lymphoma. Understanding the intricate functions of USPs in lymphoma offers new insights into potential therapeutic strategies, emphasizing the significance of these enzymes in the context of cancer biology.

Chimeric antigen receptor natural killer (CAR-NK) cell therapy is recognized as a promising modality for the treatment of hematologic malignancies, particularly B-cell malignancies. In this study, we developed ''off-the-shelf'' anti-CD19 CAR-NK cells using anti-CD19 CAR mRNAs formulated in proprietary ionizable lipid nanoparticles (LNPs). The efficiency of mRNA-LNP delivery into umbilical cord blood (UCB)-derived NK cells and primary T cells was evaluated in an in-vitro setting, demonstrating superior delivery efficiency in NK cells. Further investigation showed a probable role for an endocytic mechanism, macropinocytosis, in efficient transfection of NK cells with LNPs. Nevertheless, CAR-NK cells generated through this mRNA-LNP platform exhibited significantly enhanced cytotoxicity against CD19+ target cells, such as EGFP+Raji stable cell line and primary malignant B cells derived from refractory/relapsed B-cell acute lymphoblastic leukemia (B-ALL) patients. These findings highlight the promise of the mRNA-LNP platform in advancing CAR-NK therapies against B-cell malignancies.Competing Interest StatementThe authors V.K. and S.D. are management board member and employees at ReNAP. M.S., Ma.A., A.M., and M.S.M. are current employees at ReNAP. R.A. is former employee at ReNAP. Mo.A. is Associate Professor of Laboratory Hematology and Blood Banking; M.V. is head of research institute and Associate Professor of hematology and oncology; M.B. is assistant professor of hematology and oncology; and S.T. is PHD student at Hematopoietic Stem Cell Transplantation Research Center in Shariati Hospital, Tehran university of medical sciences. H.S.S. is medical student at medical science department of Tehran university of medical sciences. The authors declare no other relationships or activities that could appear to have influenced the submitted work.