UCL Cancer Institute Seminar Series

Professor Jan Burger,MD Anderson Cancer Centre, Houston, Texas, USA, presents: BCR signaling: insight into diease biology and therapeutic targeting in Chronic Lymphocytic Leukemia (CLL), Tuesday 27th Sept, 12pm

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B lymphocytes which are highly dependent on interactions with the tissue microenvironment for their survival and proliferation. Critical components of the microenvironment are monocyte-derived nurselike cells (NLCs), mesenchymal stromal cells, T cells and NK cells, which communicate with CLL cells through a complex network of adhesion molecules, chemokine receptors, TNF family members, and soluble factors. (Auto-) antigens and/or autonomous mechanisms activate the B-cell receptor (BCR) and its downstream signaling cascade in secondary lymphatic tissues, playing a central pathogenetic role in CLL. Novel small molecule inhibitors, including the BTK inhibitor ibrutinib and the PI3Kδ inhibitor idelalisib, target BCR signaling and have become successful new therapeutics in this disease. In this presentation I will review the cellular and molecular characteristics of CLL cells, and discuss how they engage in cellular and molecular cross-talk with their microenvironment. I will also highlight novel treatment strategies, focusing on BCR signaling inhibitors and how these treatments disrupt CLL-microenvironment interactions.

Host: Professor Bart Vanhaesebroeck

The seminar will be followed by a sandwich buffet lunch.

Selected publications

Jain P, Keating M, Thompson PA, Trinh L, Wang X, Wierda W, Ferrajoli A, Burger J, Kantarjian H, Estrov Z, Abruzzo L, O'Brien S. High FISH percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome. Am J Hematol 90(6):471-7, 6/2015. e-Pub 3/2015. PMID: 25683856

Jain P, Keating M, Wierda W, Estrov Z, Ferrajoli A, Jain N, George B, James D, Kantarjian H, Burger J, O'Brien S. Outcomes of patients with chronic lymphocytic leukemia (CLL) after discontinuing ibrutinib. Blood 125(13):2062-7, 3/2015. e-Pub 1/2015. PMID: 2557

ten Hacken E, Burger JA. Microenvironment dependency in Chronic Lymphocytic Leukemia: The basis for new targeted therapies. Pharmacol Ther 144(3):338-48, 12/2014. e-Pub 7/2014. PMID: 25050922.

For more information, see http://faculty.mdanderson.org/jan_burger/default.asp

Location

UCL Cancer Institute
Courtyard Café
Paul O'Gorman Building
72 Huntley Street
London, WC1E 6DD

This seminar has been sponsored in part by Merck, the UCLH/NIHR Biomedical Research Centre and Cancer Research UK