Protocol for the development of a bioluminescent AML-PDX mouse model for the evaluation of CAR T cell therapy.

Patient-derived xenograft (PDX) models of acute myeloid leukemia (AML-PDX) offer advantages over cell line models by capturing the complexity and heterogeneity of patient-derived samples. Here, we present a protocol for developing a bioluminescent AML-PDX model in mice to evaluate chimeric antigen receptor (CAR) T cell therapy. We describe steps for transducing, engrafting, expanding, and enriching AML-PDX cells.

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity.

Vacuolar ATPase (V-ATPase) is regarded as a possible target in cancer treatment. It is expressed in primary acute myeloid leukemia cells (AML), but the expression varies between patients and is highest for patients with a favorable prognosis after intensive chemotherapy. We therefore investigated the functional effects of two V-ATPase inhibitors (bafilomycin A1, concanamycin A) for primary AML cells derived from 80 consecutive patients.

Inhibition of a new AXL isoform, AXL3, induces apoptosis of mantle cell lymphoma cells.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma having a poor overall survival that is in need for the development of new therapeutics. In this study, we report the identification and expression of a new isoform splice variant of the tyrosine kinase receptor AXL in MCL cells. This new AXL isoform, called AXL3, lacks the ligand-binding domain of the commonly described AXL splice variants and is constitutively activated in MCL cells.

Repurposing chlorpromazine for anti-leukaemic therapy by nanoparticle encapsulation.

Treatment of acute myeloid leukaemia (AML) relies on decades-old drugs, and while recent years have seen some breakthroughs, AML is still characterised by poor prognosis and survival rate. Drug repurposing can expedite the preclinical development of new therapies, and by nanocarrier encapsulation, the number of potentially viable drug candidates can be further expanded. The anti-psychotic drug chlorpromazine (CPZ) has been identified as a candidate for repurposing for AML therapy.

Exocrine pancreas proteases regulate β-cell proliferation in zebrafish ciliopathy models and in murine systems.

Pancreatic β-cells are a critical cell type in the pathology of diabetes. Models of genetic syndromes featuring diabetes can provide novel mechanistic insights into regulation of β-cells in the context of disease. We previously examined β-cell mass in models of two ciliopathies, Alström Syndrome (AS) and Bardet-Biedl Syndrome (BBS), which are similar in the presence of metabolic phenotypes, including obesity, but exhibit strikingly different rates of diabetes.