Flow Cytometry in the Assessment of Prognosis and Novel Therapeutic Agents in Chronic Lymphocytic Leukemia (CLL). (24095)
Chronic Lymphocytic Leukemia (CLL) is an extremely heterogenous disease; while some patients may not require treatment for a decade or more others will experience rapid disease progression. Identifying those patients at risk of progression, relapse and drug-resistance has been a focus of research into the disease.
Several prognostic factors described in the literature can be evaluated by flow cytometry. Among these dysfunction of the ATM or TP53 proteins and expression of ZAP-70, CD49d or CD38 are known to correlate with features of poor risk disease. With an ever increasing understanding of the biology that drives the survival and proliferation of CLL cells it is becoming clear that these factors have crucial roles in mediating sensitivity to current frontline therapies and the interaction of the leukemic cells with the tumour microenvironment.
We routinely evaluate ATM/TP53 function and ZAP-70 and CD38 expression by flow cytometry on samples from all the CLL patients recruited to our studies. By culturing these samples in contact with stromal cells we are able to model the support conferred by the tumour microenvironment. Flow cytometry represents an important tool in our research since it enables discrimination between the leukemic and stromal cells.
Identifying those patients who represent poor risk disease cases and in vitro modelling of the tumour microenvironment enables a more accurate assessment of the potential efficacy of novel therapeutic agents for the patients most likely to be refractory to standard therapies.