Blood Cell Growth and Differentiation and the Changes Associated with Leukaemia

Research Leader: Dr Ian Lewis

Umbilical cord blood (CB) is a proven alternative source of haemopoietic stem cells (HSC) for transplantation. The major limiting factor to more widespread use of CB is the characteristic delay in engraftment.

Mesenchymal stem cells (MSCs) are derived from the non-haemopoietic elements of BM and are capable of in vitro differentiation into multiple mesodermal tissue types including osteoblasts, chondrocytes, myocytes and adipocytes.

It has been postulated that MSCs may promote HSC engraftment by enhancement of haemopoietic progenitor proliferation, haemopoietic growth factor production or facilitating homing of transplanted cells through adhesion molecules. MSCs have also been shown to be immunosuppressive and thus may promote engraftment by reducing the recipient alloimmune response.

In this project the group has characterised MSCs derived from human placenta and assessed their role in CB transplantation in a non-obese diabetic/severely immunodeficient (NOD/SCID) mouse model and compared outcomes to transplantation using two umbilical cord blood units.

Acute myeloid leukaemia (AML) is a clonal, neoplastic proliferation of immature myeloid cells of the haemopoietic system, characterised by aberrant or arrested differentiation. Immunological characterisation of leukaemic cells is important in the diagnosis and prognosis of AML and is increasingly being used in the monitoring of the disease. The presence of Minimal Residual Disease (MRD) in the bone marrow (BM) of patients with AML following chemotherapy is strongly associated with relapse of leukaemia.

Identification of patients with a high risk of relapse by MRD techniques may enable new therapeutic strategies to be offered to these individuals.