Publisher Correction: Novel immunotherapeutics against LGR5 to target multiple cancer types.

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Novel immunotherapeutics against LGR5 to target multiple cancer types.

We have developed and validated a highly specific, versatile antibody to the extracellular domain of human LGR5 (α-LGR5). α-LGR5 detects LGR5 overexpression in >90% of colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pre-B-ALL tumour cells and was used to generate an Antibody-Drug Conjugate (α-LGR5-ADC), Bispecific T-cell Engager (α-LGR5-BiTE) and Chimeric Antigen Receptor (α-LGR5-CAR). α-LGR5-ADC was the most effective modality for targeting LGR5 cancer cells in vitro and demonstrated potent anti-tumour efficacy in a murine model of human NALM6 pre-B-ALL driving tumour attrition to less than 1% of control treatment.

The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia.

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignant disorder of immature B lineage immune progenitors and is the commonest cancer in children. Despite treatment advances it remains a leading cause of death in childhood and response rates in adults remain poor. A preleukemic state predisposing children to BCP-ALL frequently arises , with an incidence far higher than that of transformed leukemia, offering the potential for early intervention to prevent disease.

The RNA editing landscape in acute myeloid leukemia reveals associations with disease mutations and clinical outcome.

Several studies have documented aberrant RNA editing patterns across multiple tumors across large patient cohorts from The Cancer Genome Atlas (TCGA). However, studies on understanding the role of RNA editing in acute myeloid leukemia (AML) have been limited to smaller sample sizes. Using high throughput transcriptomic data from the TCGA, we demonstrated higher levels of editing as a predictor of poor outcome within the AML patient samples.

Current and emerging therapeutic approaches for T-cell acute lymphoblastic leukaemia.

T-cell ALL (T-ALL) is an aggressive malignancy of T-cell progenitors. Although survival outcomes in T-ALL have greatly improved over the past 50 years, relapsed and refractory cases remain extremely challenging to treat and those who cannot tolerate intensive treatment continue to have poor outcomes. Furthermore, T-ALL has proven a more challenging immunotherapeutic target than B-ALL.

differentiation of human pluripotent stem cells into the B lineage using OP9-MS5 co-culture.

differentiation of human pluripotent stem cells (hPSCs) offers a genetically tractable system to examine the physiology and pathology of human tissue development and differentiation. We have used this approach to model the earliest stages of human B lineage development and characterize potential target cells for the initiation of childhood B acute lymphoblastic leukemia. Herein, we detail critical aspects of the protocol including reagent validation, controls, and examples of surface markers used for analysis and cell sorting.

Head injury in the elderly - an overview for the physician.

Head injury is a common cause for hospital admission and additionally 250,000 UK inpatients fall during hospital admissions annually. Head injury most commonly occurs as a result of falls from standing height in older adults. Older adults are frequently frail and multi-morbid; many have indications for anticoagulation and antiplatelet agents.

Risk-stratified adoptive cellular therapy following allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukaemia.

Following reduced intensity-conditioned allogeneic stem cell transplantation (RIC allo-SCT) for chronic lymphocytic leukaemia (CLL), there is an inverse relationship between relapse and extensive chronic graft-versus-host disease (GVHD). We evaluated outcomes in 50 consecutive patients with CLL using the approach of alemtuzumab-based RIC allo-SCT and pre-emptive donor lymphocyte infusions (DLI) for mixed chimerism or minimal residual disease (MRD), with the intention of reducing the risk of GVHD. Forty two patients had high-risk disease, including 30% with 17p deletion (17p-).

Modelling how initiating and transforming oncogenes cooperate to produce a leukaemic cell state.

Summary of and comment on a recent paper entitled ‘Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells’ (Ashton et al., 2012).

Routine bone marrow biopsy is not necessary in the staging of patients with classical Hodgkin lymphoma in the 18F-fluoro-2-deoxyglucose positron emission tomography era.

Accurate staging of classical Hodgkin lymphoma (CHL) directs treatment intensity. Functional imaging can detect marrow/bone involvement making the role of bone marrow biopsy (BMB) unclear. We assessed current UK practice in CHL staging by questionnaire and retrospectively analyzed patients staged at a single center with BMB and (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).