Von Willebrand factor and cancer; metastasis and coagulopathies.

Von Willebrand factor (VWF) is a multimeric procoagulant plasma glycoprotein that mediates platelet adhesion along the endothelium. In addition to its role maintaining normal hemostasis, more recently novel biological functions for VWF have been described, including inflammation, angiogenesis, and metastasis. Significantly increased plasma VWF levels have been reported across a variety of cancer patient cohorts.

Repression of Mcl-1 expression by the CDC7/CDK9 inhibitor PHA-767491 overcomes bone marrow stroma-mediated drug resistance in AML.

Acute myeloid leukaemia (AML) is an aggressive cancer with 50-75% of patients relapsing even after successful chemotherapy. The role of the bone marrow microenvironment (BMM) in protecting AML cells from chemotherapeutics and causing consequent relapse is increasingly recognised. However the role that the anti-apoptotic Bcl-2 proteins play as effectors of BMM-mediated drug resistance are less understood.

Three-dimensional ex vivo co-culture models of the leukaemic bone marrow niche for functional drug testing.

Acute myeloid leukaemia (AML) is a hierarchically structured malignancy in which aberrant leukemic stem cells drive the production of leukaemic blast cell clones. AML cells strictly depend on the bone marrow microenvironment (BMM) in which they reside. Classical AML cell cultures fail to mimic the BMM and, therefore, drug discovery studies are dominated by in vivo models.