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Jacqueline Boultwood

BSc (Hons), PhD

Professor of Molecular Haematology

Molecular pathogenesis of the myelodysplastic syndromes (MDS)

My research studies concern the investigation of the molecular pathogenesis of myeloid malignancies, including the myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). 

My work has focused on MDS, a heterogeneous group of clonal myeloid disorders. My studies have been instrumental in the determination of the molecular pathogenesis of several subtypes of MDS including the 5q- syndrome and refractory anaemia with ring sideroblasts (RARS). Our research identified the commonly deleted region (CDR) of the del(5q) in the 5q- syndrome and showed that p53 activation (secondary to haploinsufficiency of RPS14 mapping within the CDR) underlies the anaemia in this disorder. 

Our study of the MDS transcriptome has yielded valuable insights into the molecular pathophysiology of MDS, and has identified new prognostic markers and therapeutic targets for this disorder. More recently we have provided deep insights into how gene mutations drive the changes in the MDS transcriptome. 

Splicing factor genes are the most commonly mutated genes in MDS, and this is another important area of study. Mutation of the splicing factor SF3B1 is strongly associated with the MDS subtype RARS and our studies have implicated aberrant splicing of the downstream target gene ABCB7 in the pathophysiology of RARS. We have also identified the key target genes of the mutant splicing factor gene U2AF1 in the cell lineages affected in MDS. These data have critical implications for understanding MDS phenotypic heterogeneity and support the development of therapies targeting splicing abnormalities. 

Using next generation sequencing technology, we have illuminated the molecular landscape of MDS, and provided new insights into the genetic basis of disease progression to AML. 

We are currently using CRISPR/Cas9 genome editing to investigate the impact of common mutations on the MDS phenotype. In addition, we are using induced pluripotent stem cell (iPSC) technology and CRISPR/Cas9 to model chronic myelomonocytic leukaemia and for drug discovery.

I have served on several advisory committees and scientific panels, including Leuka and the International Working Group for the Prognosis of MDS. I am a member and trustee of the UK MDS Forum. I am a member of numerous Editorial Boards of scientific journals, including Blood and British Journal of Haematology, and Associate Editor of Molecular Biotechnology.