Research

In lymphoma our focus is a B cell malignancy called follicular lymphoma and the (epi)genomic changes responsible for the onset and severity of the disease. Although these tumours are chemo-sensitive, the disease is incurable, with many patients experiencing several episodes of relapse before the disease becomes refractory to treatment. We have traced the genetic changes in these tumours over time and uncovered a highly complex pattern of tumour evolution, consistent with the existence of a common progenitor B cell (CPC) population from which each new episode of disease is thought to arise. Current studies are focusing on characterising this CPC population and the use of KDM5 inhibition as a means of subverting the effects of mutations in the histone methyltransferase, KMT2D, that arise in >70% of FL tumours.

In leukaemia we have a longstanding interest in the study of familial acute myeloid leukaemia (AML) and myelodysplasia. These studies are important both to the individual families and are providing new insights into the molecular evolution of AML, the patterns by which mutations arise and an explanation for the clinical heterogeneity that exists both within and between families. We also have a parallel programme in poor risk AML where outcomes have changed little over the past 40 years, and are following a multi-omic strategy to profile these AMLs and gain a deeper understanding of the disease in this group of patients.  

Other Activities

• Member of the Bloodwise Grant Committee (2017-)
• Member of the Associazione Italiana per la Ricerca sul Cancro (AIRC) international fellowship committee (2016 - )
• Member of the NCRI Lymphoma CSG (2018-)
• Advisory Board Lancet Haematology
• Editor Annals of Human Genetics
• External Examiner on the BMedSCi Course, Birmingham (2016-)

Major Funding

• 2018-2023- Cancer Research UK Accelerator Award, UK & Follicular Lymphoma lead (Jesus San Miguel (Spain) and Mario Cazzola (Italy), £1.6M to UK
• 2017-2022- Cancer Research UK Programme Award, Co-PI (Improving treatment in Poor Risk Acute Myeloid Leukemia), £1.9M
• 2015-2019- Bloodwise Programme Award, Co-PI (with Dokal and Vulliamy) Genetics of Familial Leukaemia, £1.4M
• 2013-2018- Cancer Research UK, Personalised Epidgenetic Therapy for Follicular Lymphoma, £542,566.63
• 2016-2018- Bloodwise, Precision medicine for aggressive lymphoma, £340,538.00

Recent Publications

Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma. Araf S, Wang J, Korfi K et al. Leukemia (2019) (2)
https://www.ncbi.nlm.nih.gov/pubmed/30903015

GATA2 monoallelic expression underlies reduced penetrance in inherited GATA2-mutated MDS/AML. Al Seraihi AF, Rio-Machin A, Tawana K et al. Leukemia (2018) 32(2) 2502-2507
https://www.ncbi.nlm.nih.gov/pubmed/29749400

homozygous OB-fold variants in telomere protein TPP1 are associated with dyskeratosis congenita-like phenotypes DOKAL I, TUMMALA H, VULLIAMY T Blood (2018) 132(1) 1349-1353

Predicting early relapse in follicular lymphoma: have we turned a corner? Araf S, Okosun J, Fitzgibbon J Lancet Oncol (2018) 19(2) 441-442
https://www.ncbi.nlm.nih.gov/pubmed/29475722

Proteomic and genomic integration identifies kinase and differentiation determinants of kinase inhibitor sensitivity in leukemia cells. Casado P, Wilkes EH, Miraki-Moud F et al. Leukemia (2017) (2)
https://www.ncbi.nlm.nih.gov/pubmed/29229977

Follicular lymphoma: State-of-the-art ICML workshop in Lugano 2015. Gascoyne RD, Nadel B, Pasqualucci L et al. Hematol Oncol (2017) 35(2) 397-407
https://www.ncbi.nlm.nih.gov/pubmed/28378425

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors. Horton SJ, Giotopoulos G, Yun H et al. Nat Cell Biol (2017) 19(2) 1093-1104
https://www.ncbi.nlm.nih.gov/pubmed/28825697

The molecular pathogenesis of the NUP98-HOXA9 fusion protein in acute myeloid leukemia. Rio-Machin A, Gómez-López G, Muñoz J et al. Leukemia (2017) 31(2) 2000-2005
https://www.ncbi.nlm.nih.gov/pubmed/28630438

Recurrent somatic JAK-STAT pathway variants within a RUNX1-mutated pedigree. Tawana K, Wang J, Király PA et al. Eur J Hum Genet (2017) 25(2) 1020-1024
https://www.ncbi.nlm.nih.gov/pubmed/28513614

Familial CEBPA-mutated acute myeloid leukemia Tawana K, Rio-Machin A, Preudhomme C et al. SEMINARS IN HEMATOLOGY (2017) 54(11) 87-93
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404944900006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Team

Postdoctoral Researchers in this group
Dr James Heward, Dr Ana Rio-Machin, Dr Findlay Copley, Dr Eve Coulter, Dr Hannah Armes 

PhD Students
Karina Close

Clinical Research Fellows
Emil Arjun Kumar

Research Assistant
Lily Hoa

Biography

I joined Barts and the London Medical School as a Research Fellow in Medical Oncology in 1997, becoming Senior Lecturer in 2004, Reader in 2009 and Professor in 2013. I received my BA degree in Genetics at Trinity College Dublin in 1989 before completing my PhD studies on the Genetics of Tuberous Sclerosis at University College London in 1993.