Acute lymphoblastic leukaemia (ALL) is a leading cause of cancer-related death in children and young adults and arises predominantly from B-cell precursors (BCPs). Presence of the Philadelphia translocation (Ph) encoding the oncogenic BCR-ABL1 tyrosine kinase classifies the largest ALL subgroup in adults, which is historically associated with poor prognosis. Until now, allogeneic stem cell transplantation is the only curative option.

While BCR-ABL1 efficiently initiates and drives leukaemia, successful malignant transformation is associated with additional changes that facilitate the onset of leukaemia, including dampening of kinase signalling thresholds, upregulation of the unfolded protein response, changes in cell metabolism, and deregulation of B-lineage genes. The laboratory of Dr Niklas Feldhahn is investigating genetic and non-genetic (e.g. epigenetic) events that establish these changes during successful malignant transformation towards leukaemia. In addition, the Feldhahn lab is investigating sources of DNA damage that promote genetic lesions found in human B-ALL, and factors that ensure genome integrity of transformed cells in the presence of oncogene expression, such as BCR-ABL1 in Ph+B-ALL.

For further information, please visit Dr Feldhahn's Professional Web Page.

Professor Anastasios Karadimitris has developed a novel invariant NKT cell-based immunotherapeutic platform that it lends itself for the prevention of acute graft-versus-host disease and in the form of chimaeric antigen receptor-iNKT cell immunotherapy for the treatment of blood and solid tumour cancers, chronic viral diseases and autoimmune disease.

Research projects at different stages of development from pre-clinical to early clinical testing (in collaboration with the John Goldman Centre for Cell Therapy) are ongoing and it is hoped that they will help establish iNKT cell-based immunotherapy as a valuable therapeutic approach.

Understanding the biology and improving the management of chronic myeloid leukaemia (CML) has been a major focus of the group for the past four decades. Professor Jane Apperley and Dr Dragana Milojkovic co-ordinate the largest clinical practice in CML in Europe. Together they care for over 800 patients treated with tyrosine kinase inhibitors (TKI) and the survivors of more than 1000 allogeneic stem cell transplants (alloSCT) for CML. They have been pivotal in the development of the TKI for clinical use, participating in numerous pivotal phase II and III trials of all the currently available drugs. The clinical team work closely with colleagues in cytogenetics and molecular pathology (Professor Letizia Foroni, Dr Jamshid Khorashad) to optimise disease management.

Using comprehensive local and regional clinical outcome databases, together with accurate molecular monitoring, the group has made important contributions to the management of patients on TKI with respect to biomarkers, predicting responses, molecular monitoring and managing side effects. The value of our clinical data is enhanced by the presence of a CML biobank for both in-house and national use. Current academic-initiated clinical studies focus on the incidence and outcome of serious adverse events, helping patients to retain their ability to parent children whilst on treatment with TKI, the impact of kinase domain mutations on response to subsequent TKI, and devising more accurate assays to predict the patients most likely to be able to discontinue therapy after establishing a deep and durable response to TKI. Together with colleagues at the University of Liverpool, and supported by our in-house biostatistician, Dr Richard Szydlo, we now host the UK registry of clinical outcome in CML, where our focus is on ‘real-world’ management and response.

Modern management of CML, either by TKI or SCT, now requires rigorous attention to monitoring or minimal residual disease (MRD). The Department was the originator of PCR based monitoring for disease response. Originally developed to recognise early relapse after transplant the technique has been adopted globally to monitor patients on TKI. Our molecular diagnostic and MRD laboratory is internationally acclaimed for accuracy and quality, such that we support the molecular monitoring of global commercial and national academic studies. Our research group has a particular interest in the identification of biomarkers for response to therapy and disease progression. We combine our expertise in next-generation sequencing (NGS) and gene expression profiling with studies in epigenetics in an attempt to identify patients less likely to respond to TKI so that alternative therapy can be offered as early as possible in their disease course. Our work now forms part of the newly formed Global Alliance in CML, that will combine the genomic, transcriptomic and epigenetic results from major laboratories worldwide, to better understand the molecular mechanisms underlying response or resistance to TKI, and progression to advanced phase disease.

The use of TKI has replaced the previous front line therapy of alloSCT, nevertheless, the department remains the busiest centre in Europe for SCT in CML, as we maintain a national and international referral service for patients failing TKI. We have a comprehensive clinical database of transplant outcome, co-ordinated Dr Richard Szydlo, and have contributed extensively to improvements in clinical management and outcome.

The use of TKI has replaced the previous front line therapy of alloSCT, nevertheless, the department remains the busiest centre in Europe for SCT in CML, as we maintain a national and international referral service for patients failing TKI. We have a comprehensive clinical database of transplant outcome, co-ordinated by our in-house biostatistician, Dr Richard Szydlo, and have contributed extensively to improvements in clinical management and outcome.

The study of the pathobiology of haematological malignancies is a key research area. Professor Kikkeri Naresh and his associates in the Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) play a key role in driving translational research in lymphomas and lymphoproliferative disorders, and bone marrow based haematological malignancies. They also support other research programmes in the Centre for Haematology.

Professor Naresh’s group and his collaborators have been involved in studying the genomics of various B cell and T cell lymphomas and immune deficiency lymphoproliferative disorders including those in HIV and post-transplant settings. Their work has also extended to understanding the role played by the microenvironment in B cell lymphomas and Hodgkin lymphoma. The group’s work has led to the design of diagnostic algorithms, including those that could be applicable in countries with limited resources. Refining criteria for diagnosis, the discovery of immunohistochemical markers for diagnosis and of biomarkers for disease stratification are other key areas that have been studying.

Human T-lymphotropic virus type-1 (HTLV-1) infects CD4+ T-cells and causes either adult T-cell leukaemia/lymphoma (ATL) or an HTLV-1 associated myelopathy (HAM) in approximately 5%-10% of carriers. The National Centre for Human Retrovirology, founded by Professor Graham Taylor in 2004, is based at Imperial College Healthcare NHS Trust and receives clinical referrals from across the country for all patients with HTLV-1 infection. Initially, a research clinic established in 1993 by Imperial College to study the natural history and pathogenesis of HTLV- infections the clinic has expanded to meet the growing need to provide specialized multidisciplinary services for the rare conditions associated with these infections. The clinical cohort has expanded since the introduction of universal screening of blood donors in 2002. The UK lead for ATL is Dr Lucy Cook who offers a dedicated weekly clinic offering novel diagnostics, treatment options and clinical trials for ATL.

There are strong research links with Professor Charles Bangham’s HTLV-1 group at Imperial College London with a central aim is to produce qualitative and quantitative understanding of the persistence of HTLV-I and the immune response to HTLV-I, and an explanation of why certain individuals infected with HTLV-I develop fatal or disabling diseases while the majority remain asymptomatic using a broad range of techniques in molecular and cellular immunology, viral and host genetics, cell biology, DNA expression microarrays, proteomics and mathematics.

Professor Anastasios Karadimitris and Dr Aristeidis Chaidos have established a lab-based research programme aiming to uncover novel aspects in the biology of multiple myeloma. They are specifically interested in the role of transcriptional and epigenetic deregulation in the pathogenesis of multiple myeloma, osteoclast activation and myeloma bone disease. Through understanding of these processes they aspire to define new therapeutic targets and hopefully develop relevant therapeutic agents.

Dr Chaidos also has a clinical and laboratory-based research interest in the pathogenesis and management of myeloma kidney disease and monoclonal gammopathy of renal significance (MGRS), working in collaboration with Renal Medicine and Renal Pathology and with the International Kidney & Monoclonal Gammopathy Research Group (IKMG). An active clinical research portfolio in myeloma, led by Dr Aris Chaidos, includes national and international clinical trials of novel myeloma therapeutics.

Professor Karadimitris is also developing a chimaeric antigen receptor- invariant NKT cell immunotherapy platform for the treatment of multiple myeloma.

Their work is performed under the auspices of the newly founded Hugh & Josseline Langmuir Centre for Myeloma Research.

Dr Holger Auner is the Imperial College London representative in the Myeloma UK Clinical Trials Network, the UK Myeloma Research Alliance, and the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation (EBMT). The clinical research portfolio that is led by Dr Auner includes early and late-stage trials of novel agents including proteasome and nuclear export inhibitors.

Dr Auner's primary research interest is to better understand aspects of protein degradation pathways in multiple myeloma and other cancers, with the ultimate goal of finding novel therapeutic approaches. Dr Auner's lab, the Cancer Cell Protein Metabolism group also investigates the role of intracellular protein metabolism in bone formation. For further information, visit Dr Auner's Professional Web Page.