Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/63467
Title: Pharmacogenomic reactivation of foetal haemoglobin
Authors: Grech, Laura
Keywords: Fetal hemoglobin
Thalassemia -- Malta
Pharmacogenomics
Gene amplification
Issue Date: 2012
Citation: Grech, L. (2012). Pharmacogenomic reactivation of foetal haemoglobin (Bachelor’s dissertation).
Abstract: Foetal 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 wellknown 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 5Aza-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.
Description: B.SC.(HONS)APP.BIOMED.SCI.
URI: https://www.um.edu.mt/library/oar/handle/123456789/63467
Appears in Collections:Dissertations - FacHSc - 2012
Dissertations - FacHScABS - 2012

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