Understanding inter-patient heterogeneity in acute leukemias - insights from mathematical modeling
Thomas Stiehl
Institute for Applied Mathematics, Heidelberg University Germany
Co-Author(s): Anthony D. Ho, Christoph Lutz, Anna Marciniak-Czochra
Abstract:
Acute leukemias are cancerous diseases of the blood forming (hematopoietic) system. A hallmark of acute leukemias is their clinical heterogeneity. Leukemias are derived from a leukemic stem cell (LSC) population that out-competes hematopoietic stem cells (HSC) which are required for blood cell formation. Experiments suggest that differences in the interaction between healthy and malignant cells contribute to the inter-patient heterogeneity. These interactions include leukemic cell response to endogenous growth factors and competition of stem cells for spaces in a supportive niche. We develop nonlinear ordinary differential equation models to study the impact of these interactions on inter-patient heterogeneity.\
Combining analytical results, computer simulations and patient data analysis we provide insights into the following clinically relevant questions:
\begin{itemize}
\item What can we learn about leukemic cell regulation based on clinical data? How does it differ between patients? What is the clinical impact of the inter-individual differences?
\item Do leukemic cells require endogenous growth factors to expand or do they grow independently of regulatory signals? Does this make a difference for the clinical course and patient survival?
\item How does competition inside the stem cell niche affect disease dynamics and treatment response?
\item How can we use mathematical models to assess patient prognosis?
\end{itemize}