Genetic and cellular intratumor heterogeneity as predictor of chronic lymphocytic leukemia outcome and treatment resistance. (Stamatopoulos K: Principle Investigator (5%)
Funding Body: EUROPEAN COMMISSION
The clinical course and eventual outcome of Chronic Lymphocytic Leukemia (CLL) patients is highly variable. It is accepted that intratumor genetic and cellular heterogeneity is the main force driving both tumor development and treatment resistance. At the genetic level, there is no single gene mutation characteristic of the disease and CLL cells in a given patient may carry different burden of different mutations affecting different pathways. At the cellular level, leukemic cells remain responsive to multiple stimuli originating from microenvironment but with different intensity and effect. Available biomarkers aiming at predicting both the disease course and the response to treatment exist, but none of the current models capture the complexity of intratumor heterogeneity.
Intratumor genetic and cellular heterogeneity of CLL has tremendous implications for treatment and outcome, but is currently poorly understood. Novel means of observing and quantifying this heterogeneity together with integrative and predictive mathematical modeling will help identifying strategies to prevent treatment resistance.