My research group works on molecular pathology, genetics and progression of leukaemia and lymphomas, aiming to improve on current diagnostic, prognostic and treatment strategies.
Recurrent mTORC1-activating RRAGC mutations in follicular lymphoma. Nat Genet (2016) 48(2):183-8. PMID: 26691987
Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood (2015) 126(10):1214-23. PMID: 26162409
Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet (2014) 46(2):176-81. PMID: 24362818
Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med (2004) 351(23):2403-7. PMID: 15575056
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.
Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma. Araf S, Wang J, Korfi K et al. Leukemia (2019) (2)
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
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
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)
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
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
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
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
Familial CEBPA-mutated acute myeloid leukemia Tawana K, Rio-Machin A, Preudhomme C et al. SEMINARS IN HEMATOLOGY (2017) 54(11) 87-93
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.