Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease. One reason for the heterogeneity may originate from inter-individual differences in the responses of leukemic cells to endogenous cytokines. On the basis of mathematical modeling, computer simulations and patient data, we have provided evidence that cytokine-independent leukemic cell proliferation may be linked to early relapses and poor overall survival. Depending whether the model of cytokine-dependent or cytokine-independent leukemic cell proliferation fits to the clinical data, patients can be assigned to two groups that differ significantly with respect to overall survival. The modeling approach further enables us to identify parameter constellations that can explain unexpected responses of some patients to external cytokines such as blast crisis or remission without chemotherapy.
Highlights
Acute myeloid leukemias (AML) comprise a heterogeneous group of malignant diseases
We focus on the following questions: (i) How does time evolution of blasts differ in mathematical models of cytokine-dependent and cytokine-independent AML? (ii) Does it have a prognostic impact if patient data fits to the model of cytokine-dependent or to the model of cytokine-independent AML? (iii) Which cell parameters determine whether cytokine administration may have negative, neutral or positive effects on the leukemic cell load?
Since acute myeloid leukemia (AML) is a disease of the myeloid lineage, our models focus on the granulopoietic branch of the hematopoietic system
Summary
Acute myeloid leukemias (AML) comprise a heterogeneous group of malignant diseases. Since major clinical symptoms originate from impairment of healthy blood cell production, it is important to understand how leukemic cells interfere with healthy hematopoiesis. The correlation between cytokine-dependence in cell culture and patient survival suggests that cytokine dependence of leukemic cells may be a clinically meaningful parameter[4,5] It can depend on the culture conditions whether a leukemia sample exhibits autonomous growth or not[3]. Studies in AML patients suggest that leukemic cells can be recruited into cell cycle in response to administered cytokines[6,10,15], multiple clinical trials imply that supportive cytokine treatment has no negative effects on relapse free survival[6]. There exist reports of patients achieving complete remission solely by cytokine administration without chemotherapy[21,22,23,24] Both phenomena, negative and positive impact of cytokines on leukemic cell load, are so far not well understood. We focus on the following questions: (i) How does time evolution of blasts differ in mathematical models of cytokine-dependent and cytokine-independent AML? (ii) Does it have a prognostic impact if patient data fits to the model of cytokine-dependent or to the model of cytokine-independent AML? (iii) Which cell parameters determine whether cytokine administration may have negative, neutral or positive effects on the leukemic cell load?
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
