Erratum: Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity.

[This corrects the article DOI: 10.1016/j.omtm.

Development of a gene edited next-generation hematopoietic cell transplant to enable acute myeloid leukemia treatment by solving off-tumor toxicity.

Immunotherapy of acute myeloid leukemia (AML) has been challenging because the lack of tumor-specific antigens results in "on-target, off-tumor" toxicity. To unlock the full potential of AML therapies, we used CRISPR-Cas9 to genetically ablate the myeloid protein CD33 from healthy donor hematopoietic stem and progenitor cells (HSPCs), creating tremtelectogene empogeditemcel (trem-cel). Trem-cel is a HSPC transplant product designed to provide a reconstituted hematopoietic compartment that is resistant to anti-CD33 drug cytotoxicity.

Cell-Extrinsic Differentiation Block Mediated by EphA3 in Pre-Leukaemic Thymus Contributes to Disease Progression.

We recently characterised the () mouse as a model of T-cell pre-leukaemia, featuring thymocytes that can engraft in recipient animals and progress to T-cell acute lymphoblastic leukaemia (T-ALL). However, loss of this engraftment ability by deletion of did not result in any loss of leukemogenesis activity. In the present study, we observe that thymocytes overexpress EPHA3, and we characterise thymocyte behaviour in mice with deletion of , which show a markedly reduced incidence of T-ALL.

React, reset and restore: Adaptation of a large inflammatory bowel disease service during COVID-19 pandemic.

Introduction: Healthcare organisations have had to make adaptations to reduce the impact of the Coronavirus 2019 (COVID-19) pandemic. This has necessitated urgent reconfiguration within inflammatory bowel disease (IBD) services to ensure safety of patients and staff and seamless continuity of care provision.

Aim: To describe the adaptations made by a large inflammatory bowel disease service, caring for over 3,500 IBD patients, in response to the COVID-19 pandemic.

Practice pattern variability in the management of acute severe colitis: a UK provider survey.

Introduction: Lack of comparative trial data on dosing regimens of infliximab in patients with acute severe ulcerative colitis (ASUC) failing intravenous corticosteroids has resulted in variability of rescue regimes in ASUC with potential impact on clinical outcomes. We aimed to evaluate practice variability and physician perspectives in decision-making with rescue therapy.

Methodology: An internet-based survey of members of the inflammatory bowel disease (IBD) section of the British Society of Gastroenterology was conducted.

Endothelial E-selectin inhibition improves acute myeloid leukaemia therapy by disrupting vascular niche-mediated chemoresistance.

The endothelial cell adhesion molecule E-selectin is a key component of the bone marrow hematopoietic stem cell (HSC) vascular niche regulating balance between HSC self-renewal and commitment. We now report in contrast, E-selectin directly triggers signaling pathways that promote malignant cell survival and regeneration. Using acute myeloid leukemia (AML) mouse models, we show AML blasts release inflammatory mediators that upregulate endothelial niche E-selectin expression.

Budesonide treatment for microscopic colitis: systematic review and meta-analysis.

Microscopic colitis (MC), encompassing lymphocytic and collagenous colitis, is a common cause for chronic nonbloody diarrhoea, which impacts significantly on the quality of life for patients. Despite increasing awareness of the condition and its treatment, there is considerable variation in therapeutic approaches. To conduct a systematic review and meta-analysis on the efficacy and safety of budesonide in the treatment of MC.

Anti-tumour effects of antibodies targeting the extracellular cysteine-rich region of the receptor tyrosine kinase EphB4.

EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer.

EphB4 localises to the nucleus of prostate cancer cells.

The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4.

Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases.

The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists.

Eph receptors and their ligands: promising molecular biomarkers and therapeutic targets in prostate cancer.

Although at present, there is a high incidence of prostate cancer, particularly in the Western world, mortality from this disease is declining and occurs primarily only from clinically significant late stage tumors with a poor prognosis. A major current focus of this field is the identification of new biomarkers which can detect earlier, and more effectively, clinically significant tumors from those deemed "low risk", as well as predict the prognostic course of a particular cancer. This strategy can in turn offer novel avenues for targeted therapies.

Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand.

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion.