UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://www.um.edu.mt/events/scisem/
Email: scisem@um.edu.mt
Abstract form
Title: Drug induced alternative splicing of the PPP2CA mRNA in
haematopoietic cell lines
Presenter: Stephanie Gauci
Contact address:
Tel: 79270981
Fax:
Email: stefani.gauci@gmail.com
Presentation date: 19th May 2014
Abstract
Maintaining haematopoiesis is an essential process whereby various cells are
mandatory depending on the physiological demand. The proliferation, differentiation,
maturation and self-regeneration of this multifaceted system are under stringent
control of transcription and growth factors. Previous studies have correlated the
aberrant regulation of genetic expression such as alternative splicing to be
accountable for abnormal haematopoiesis including CMLs. Previous studies
established that 15% of CML patients of unknown clinical history revealed isoform
switching in the PPP2CA gene.
The aim of this study was to (1) create a cellular model to identify isoform switch in
the PPP2CA gene; (2) investigate splicing factor regulation in treated cells and (3)
investigate findings using CML patient samples. Several leukaemic cells lines were
treated with four drugs to create cellular model with isoform switch. PPP2CA∆5 was
characterised in amirolide treated BCR/ABL+ cells unlike BCR/ABL negative bone
marrow samples. The regulation of various splicing factors acting on these cells
were analysed by qRT-PCR. Quantification of four of the splicing factors were done
using CML patient samples expressing predominant mutant or wild-type PPP2CA.
Results indicated that amirolide drug altered alternative splicing in BCR-ABL+ cell
models by regulation of several splicing factors resulting in different PPP2CA mRNA
isoforms.