Homing to the central nervous system is associated with differential expression of selectins, integrins and chemokine receptors in pre-B acute lymphoblastic leukaemia cell lines

Williams, M.T., Graham, G. , Gibson, B. and Halsey, C. (2011) Homing to the central nervous system is associated with differential expression of selectins, integrins and chemokine receptors in pre-B acute lymphoblastic leukaemia cell lines. In: 51st Annual Scientific Meeting of the British Society for Haematology, Brighton, UK, 4-6 April 2011, pp. 1-88. (doi:10.1111/j.1365-2141.2011.08609.x)

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Abstract

Despite massive advances in the treatment of paediatric acutelymphoblastic leukaemia (ALL) challenges remain. Disease in thecentral nervous system (CNS) continues to pose difficulties indiagnosis, prevention and treatment. Understanding the biological mechanisms of leukaemic cell entry into the CNS should allow betterdetection and monitoring of leukemia and may identify noveltherapeutic targets for resistant disease. We hypothesize thatleukaemic cell dissemination to the CNS is associated with theabnormal expression of molecules governing physiological leukocytetrafficking i.e. chemokine receptors, selectins and integrins.This study compared gene, protein and functional expression ofcandidate trafficking molecules expressed by CNS homing and CNSnon-homing ALL cell lines in vitro. Initial screening for candidategene expression was performed using Taqman low density quanti-tative PCR arrays. Promising candidates were further evaluated byflow cytometry and functional assays. Clear differences were seenbetween the cell lines. CNS homing cells expressed higher levels ofchemokine receptors, integrins and selectins associated withphysiological entry of leukocytes across the blood:CSF barrier. Incontrast, CNS homing cells showed much lower levels of CXCR4expression, with reduced chemotaxis in response to the CXCR4ligand CXCL12. Since functional CXCR4-CXCL12 interactions areknown to be important for retention of cells in the bone marrowmicroenvironment, disruption of this interaction may be a necessarypre-requisite for cell migration to other sites.In conclusion, these studies support our hypothesis that theability of leukemic cells to enter the CNS is governed by theexpression patterns of leukocyte trafficking receptors.

Item Type:Conference Proceedings
Additional Information:Published in British Journal of Haematology, Volume 153, Issue Supplement s1, pages 1–88, April 2011
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Halsey, Professor Chris and Williams, Dr Mark and Gibson, Professor Brenda and Graham, Professor Gerard
Authors: Williams, M.T., Graham, G., Gibson, B., and Halsey, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:British Journal of Haematology
Publisher:Blackwell Publishing
ISSN:0007-1048
ISSN (Online):1365-2141

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