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Nov 26, 2018

Seminar - Leukemic initiating cells require bone marrow retention to induce myeloid leukemia (Speaker: Professor Reinhard Fässler)

Professor Reinhard Fässler
Department of Molecular Medicine
Max Planck Institute of Biochemistry, Germany
Mok Hing-Yiu Distinguished Visiting Professor, HKU

Date: Monday, 26-November-2018
Time: 5:00 p.m.
Venue: Seminar Room 1, G/F, Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Pokfulam, Hong Kong

Acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) are hematopoietic malignancies of the myeloid lineage characterized by abnormal proliferation and differentiation of transformed hematopoietic stem and/or precursor cells, called leukemia initiating cells (LICs) or leukemic stem cells (LSCs).

Normal hematopoietic stem and progenitor cells (HSPCs) as well as LICs receive biochemical and biophysical signals from the BM microenvironment that ensure their BM retention, self-renewal, regeneration and differentiation. The positioning and retention of HSPCs and LICs within the BM critically depends on integrin-mediated adhesion to extracellular matrix (ECM) proteins such as fibronectin (FN) and cell surface-presented ligands such as VCAM-1. Professor Fässler’s team have recently shown that BM retention and survival of dividing HSCs and progenitor cells (HSPCs) depends on Kindlin-3 (K3), which is exclusively expressed in hematopoietic cells where it binds to and activates integrins and thereby enables integrin-ligand binding, HSPC adhesion and signaling. Since the transformation of HSCs into LICs is inevitably associated with cell proliferation, they tested whether K3 may also be required to retain LICs in the tumor promoting BM microenvironment. The results of this study will be discussed at the seminar.