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Dr Ingo Ringshausen

128 Ringshausen headshot2Dr Ingo Ringshausen

Haematopoietic stem cells and malignancies

Email: ir279@cam.ac.uk

Laboratory:Cambridge Stem Cell Institute, Clifford Albutt Building, Cambridge Biomedical Campus.  

Departmental Affiliation: Department of Haematology

 

Research

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in western countries. Although CLL is a putative mature B cell malignancy, it has very recently been shown that the maturation of CD34+CD38- HSPC from CLL patients is skewed towards the lymphoid linage. Importantly, the majority of stem and progenitor cells from CLL patients carry disease specific mutations in NOTCH1, SF3B1, TP53 and XPO. These recent reports suggest that the initial oncogenic events can occur at the earliest stages of B cell specification in the stem cell compartment. 

Our group previously demonstrated that malignant cells actively re-program mesenchymal stromal cells, a process that is dependent on the activation of NF-κB and essential for disease propagation. We are now interested in understanding how clonal evolution from a pre-malignant progenitor to a treatment-resistant B cell malignancy affects the activation and reprogramming of niche cells in the bone marrow microenvironment and how this contributes to microenvironment-mediated drug resistance. Related to this, we are investigating how the lymphoma-remodelled microenvironment impairs normal HSC biology, leading to bone marrow failure.

 

Group Members

Maurizio Mangolini, Andrew Moore, Eugene Park, Antonella Santoro, Vijitha Sathiaseelan, Ash Sundaresh.

 

Plain English

Similar to normal blood stem cells, malignant cells from patients with B cell lymphomas require signals from their surrounding environment for cell survival and proliferation. Thus, benign bystander cells provide crucial support for malignant cells, mediated by direct cell-cell contact and soluble factors. Understanding these cell-cell communications from a molecular viewpoint opens new directions to treat blood-born malignancies. Specifically, we want to understand: 1. How this cell-cell communication changes over time? Are malignant cells from patients with relapsed disease equally dependent on these signals? 2. How does this communication between malignant cells and their micro-environment affects the function of normal haematopoietic stem cells and the production of normal blood cells?

 

Key Publications