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Bone Marrow Failure & Myelodisplastic Syndromes

The Bone Marrow Failure (BMF) Team specialises in comprising acquired aplastic anaemia (AA), myelodysplastic syndromes (MDS) and paroxysmal nocturnal haemoglobinuria (PNH). Collectively these disorders are chronic, associated with considerable morbidity and mortality and more likely to transform to MDS/acute myeloid leukaemia (AML).

Our group consists of a dedicated team of scientists and clinicians with access to state of the art equipment which enables us to study wide-spectrum of aspects of bone marrow failure syndromes including; karyotyping by SNP analysis, expression profiling of mRNA and microRNA, mutation analysis by next generation sequencing, DNA damage repair and immunoregulation.

King’s College Hospital (KCH) is unique in the UK and the rest of Europe in providing national and international clinical and research expertise in these disorders. Our clinical partners, the adult haemopoietic stem cell/bone marrow transplant unit at King’s College Hospital are the largest in the UK and the only one to provide a specialist service for AA.

Members

Joop Gaken

Joop Gaken

Senior Scientist

haematological malignancies

Involvement of transposable elements in Haematological Malignancies

A very large percentage of the human genome consists of repetitive sequences. One of these are the Line elements which form 20% of the human genome and are derived from retrotransposons. The majority of these elements are silenced due to accumulated mutations but a small number can be reactivated. This project will investigate the possible role of this re-activation in the induction of haematological malignancies.

CAR t cell therapy

Cytokine release syndrome and allogeneic anti-CD123 chimeric antigen receptor T-cell therapy for acute myeloid leukaemia

Following the success of CAR T-cell therapy in treatment of B-cell malignancies, this approach is being explored across a range of cancers, including acute myeloid leukaemia (AML). However, CAR T-cells and other immunotherapies can cause major toxicity in the form of cytokine release syndrome (CRS). CRS is thought to result from activation of host monocytes/macrophages, but the details of this process are not well characterised. By modelling the behaviour of healthy and malignant monocytic cells during CRS, we aim to identify new methods for prediction, prevention and treatment – both in the context of AML and more broadly.

blood vessels

Eltrombopag in Aplastic Anemia

This is focused on the genomics sequencing and analysis for RACE, which is a phase III randomized trial in aplastic anemia (AA), examining the effectiveness of eltrombopag plus immunosuppressive therapy (IST) vs IST alone as a frontline therapy for AA. We perform Illumina sequencing using targeted gene panels on samples from baseline, 6 months post treatment, and 24 month follow up, which allows us to observe clonal behaviour over time. We aim to find signatures that indicate a patients' chances of responding poorly to therapy, to better identify priority candidates for allogeneic therapy.

TIARA T-cell 224x135

TIARA: Production of expanded autologous regulatory T cells to treat patients with aplastic anaemia: A phase I study

TIARA trial, is the first human phase I/II trial in the world to treat refractory AA patients. Expanded autologous Tregs have now been prepared in GMP facilities and therapeutically used in Phase 1 clinical trials to treat autoimmune disorders Work done by our group has shown reduced percentage of autologous regulatory cells (Tregs) in AA patients. For TIARA autologous Tregs will be expanded from group of patients for whom there has not been much advancement in treatment. The aim is to determine the potential of Tregs in controlling the abnormal immune response.

Key Group Publications

  • Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia

    Régis Peffault de Latour, M.D., Ph.D., Austin Kulasekararaj, M.D., Simona Iacobelli, Ph.D., Sofie R. Terwel, M.Sc., Riley Cook, B.Sc., Morag Griffin, M.D., Constantijn J.M. Halkes, M.D., Christian Recher, M.D., Ph.D., Fiorenza Barraco, M.D., Edouard Forcade, M.D., Ph.D., Juan-Carlos Vallejo, M.D., Beatrice Drexler, M.D., et al., for the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation*. In: New England Journal of Medicine. 
View all publications

Dr Henry Wood

Mr Riley Cook

Miss Manar Alfaham

Contact us

Professor Ghulam Mufti - Group Leader of the Bone Marrow Failure & Myelodisplastic Syndromes Group

Joop Gaken - Scientist in the Bone Marrow Failure & Myelodisplastic Syndromes Group