Mechanisms of leukemic stem cell interaction in AML: insights from complementary mathematical modeling approaches

Acute myeloid leukemia (AML) is a severe disorder of the blood forming system which is commonly treated with cytotoxic drugs. It is still incompletely understood how the dynamic interaction between leukemia and the stem cell-niche influences AML progression, treatment outcome and resistance formation. To investigate different assumptions about these regulations, especially with respect to stem cell proliferation, we compare two recently published, complementary ODE models of AML progression and treatment. We assess the models’ suitability to describe disease dynamics and treatment outcomes by fitting each model to 275 clinical remission time courses and respective therapy cycles. Furthermore, we perform a systematic screening with univariate alterations for relevant parameters to evaluate their influence on several metrics.

We conclude that the regulation of normal and leukemic stem cell proliferation can be coupled to niche-dependent and niche-independent mechanisms. While both assumptions allow to sufficiently describe clinically available time course data, their complementary roles in leukemia progression but also in normal and stress hematopoiesis need to be further delineated.

Involved scientists

• Christoph Harnisch
• Dr Friedemann Uschner
• Prof Dr Ingo Röder
• Prof Dr Ingmar Glauche

Cooperation Partner

• Prof Artur C. Fassoni (Instituto de Matemática e Computação, Universidade Federal de Itajubá, Itajubá, Brazil)

Funding

IMB budget