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dc.identifier.citationGrech L. (2012). Pharmacogenomic reactivation of foetal heamoglobin (Bachelor's dissertation).en_GB
dc.description.abstractPoctal haemoglobin (HbF) production in humans is controlled by many intricate mechanisms that to date remain partly understood. Pharmacogenomic studies aimed at understanding how particular compounds are able to induce HbF may help to elucidate the molecular control of globin switching. In this study, a collection of Maltese β-thalassaemia homozygotes and compound heterozygotes, healthy adults and KLF 1-haploinsufficient adults from Malta were explored. The effects of hydroxyurea (HU), thalidomide and 5-Aza-2'-deoxycytidine, all well-known HbF inducing agents, were studied in an effort to identify whether they augment HbF and to what extent. Of all the groups tested, the fold change increase of HbF was not always easy to interpret since the β-thalassaemia homozygotes and compound heterozygous patients and the KLF 1 haploinsufficient patient had a higher HbF to start off with as a baseline and hence fold change increase tended to be somewhat lower than in the healthy adults. The data presented here underline for the first time a role for KLF 1 inhibition by drugs in culture (in vitro) in human haematopoiesis and suggest that the KLF 1 gene may be an important pharmacogenomic marker to predict efficacy to HU, thalidomide or 5-Aza-2'-deoxycytidine treatment. Comparisons conducted between different HbF expression profiles across the three groups, that included low and high HbF scenarios and "responders" versus "non-responders" for HU, thalidomide and 5- Aza-2' -deoxycytidine treatment, the augmentation of HbF may be partially explained by down regulation of KLF 1. Drugs in culture have inhibited this gene, and more or less provided similar evidence to the results obtained across multiple testing scenarios and different groups. The effect on HbF by the drugs in culture was evident at 24 hrs in the healthy adults whilst more pronounced at 72 hrs for the β-thalassaemia homozygotes and compound heterozygous patients and the KLF1 haploinsufficient patient.en_GB
dc.subjectPharmacogenomics -- Maltaen_GB
dc.subjectHemoglobin -- Maltaen_GB
dc.titlePharmacogenomic reactivation of foetal heamoglobin.en_GB
dc.rights.holderThe copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holderen_GB
dc.publisher.institutionUniversity of Maltaen_GB
dc.publisher.departmentFaculty of Health Sciences. Department of Applied Biomedical Scienceen_GB
dc.contributor.supervisorBorg, Joseph-
dc.contributor.creatorGrech, Laura-
Appears in Collections:Dissertations - FacHScABS - 2012

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