1 Hæmatologisk Afdeling, Aalborg Sygehus, Faculty of Health Sciences, Aarhus University, Aarhus University2 Department of Clinical Medicine, Health, Aarhus University3 Department of Clinical Medicine, Health, Aarhus University
Test of the hypothesis; a lymphoma stem cell exist which is capable of self-renewal Malene Krag Pedersen, Karen Dybkaer, Hans E. Johnsen The Research Laboratory, Department of Haematology, Aalborg Hospital, Århus University Failure of current therapeutics in the treatment of diffuse large B-cell lymphomas (DLBCL) may be related to the resistance and persistence of a putative lymphoma stem cell compartment. Cancer stem cells are capable of initiating and sustaining the tumour and share some characteristics with normal stem cells. Cancer stem cells and normal stem cells are both low frequent and have the ability to self-renew, which involves control of cellular processes such as cell cycle, apoptosis and differentiation. Gene expression analyses on isolated cancer stem cells and early progenitor cells provide a strong tool for studying the molecular events characteristic for the cancer initiating and sustaining cells(1-3). My project is based on studies of stem and early progenitor cells in lymphoid cell lines from patients with advanced DLBCL. The cell lines are world wide recognised and generously provided by Dr. Hans Messner and colleagues. Hypothesis and aims: A lymphoma stem and progenitor cell compartment exists, which is capable of self-renewing. This compartment within the two subgroups of DLBCL, activated B-cell-like (ABC) and germinal center B-cell-like (GCB), has some stem cell gene expression similarities and differences. The aims of the study are; 1) To estimate the frequency of lymphoma cell line clonogenic cells (stem cells) by limiting dilution. 2) To characterise and sort the clonogenic cell population by FACS. 3) To generate single cell cDNA archives on the sorted cells by global RT-PCR. 4) To analyse the expression level of distinct stem cell genes on the sorted cells by qRT-PCR. (1) Bonnet D. Normal and leukaemic stem cells. Br J Haematol 2005 Aug;130(4):469-79. (2) Huntly BJ, Gilliland DG. Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 2005 Apr;5(4):311-21. (3) Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001 Nov 1;414(6859):105-11.
Kræftstamceller, selv-fornyelse, B-celler, lymfom; cancer stem cell, self-renewal, B-cells, lymphoma