Acute myeloid leukaemia (AML) is highly heterogeneous haematological malignancy, which represents a challenge in the understanding of the disease. Relapse in AML is common, andmany relapsed patients respond poorly to conventional treatment, leading to a low survivalrate. Investigating the mutational landscape connected to relapse AML is therefore of highinterest in order to improve clinical outcome. Recurrent in-frame internal tandem duplications(ITDs) in exon 13 of the UBTF gene have previously been discovered in paediatric relapseAML, correlating to one of the DNA binding domains of the transcription factor UBTF.UBTF is involved in recruitment of RNA polymerase I and activation of the transcription ofribosomal RNA. As a result, it is an important factor in ribosome biogenesis. In this study, wehave investigated the effect of UBTF-ITDs on RNA synthesis and UBTF localization. I haveshown that ITDs lead to disturbed localization of UBTF to the nucleus, which coupled withthe previous finding that patients are heterozygous for the ITDs, indicates haploinsufficiency.This could have potential implications in AML drug resistance. We have further generated anin vitro model for investigating the effect of UBTF haploinsufficiency, which could lead toidentification of vulnerabilities to be targeted in future drug treatments.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-474435 |
| Date | January 2022 |
| Creators | Paulsson, Annie |
| Publisher | Uppsala universitet, Institutionen för biologisk grundutbildning |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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