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Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
Contribution to the study of periodic chronic myelogenous leukemia
Laurent Pujo-Menjouet1, Michael C Mackey
1Department of Physiology, Centre for Nonlinear Dynamics, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada H3G 1Y6. pujo@cnd.mcgill.ca
Insights
Periodic chronic myelogenous leukemia (PCML) exhibits long oscillations (40-80 days) compared to stem cell cycles. A G0 model suggests stem cell dynamics may explain these extended PCML periods.
Area of Science:
- Mathematical biology
- Hematology
- Cell cycle dynamics
Background:
- Periodic chronic myelogenous leukemia (PCML) displays oscillations with periods significantly longer than the hematopoietic stem cell cycle.
- The underlying mechanisms driving these long-period oscillations remain incompletely understood.
Purpose of the Study:
- To investigate the origin of long-period oscillations observed in periodic chronic myelogenous leukemia (PCML).
- To utilize a G0 model for stem cell dynamics to analyze PCML periodicity.
Main Methods:
- Analysis of local stability conditions within the G0 stem cell model.
- Investigation of Hopf bifurcation conditions.
- Parameter role interpretation in stability loss.
- Examination of a simplified model to infer stem-cell level changes.
Main Results:
- The study determines local stability conditions for the G0 stem cell model.
- Conditions under which Hopf bifurcation can occur are identified.
- The influence of individual parameters on stability loss is elucidated.
Conclusions:
- Stem cell dynamics, modeled using a G0 approach, offer a potential explanation for the extended oscillation periods in PCML.
- Specific changes at the stem-cell level may account for the characteristic PCML oscillations.
Abstract:
The period (in the order of 40 to 80 days) in periodic chronic myelogenous leukemia (PCML) oscillations is quite long compared with the duration of the cell cycle of the hematopoietic stem cells from which the oscillations are presumed to originate (in the order of one or two days). Our objective is to understand the origin of these long-period oscillations using a G0 model for stem cell dynamics. We determine the local stability conditions and show under what conditions the Hopf bifurcation may occur. We interpret the role of each parameter in the loss of stability, and then examine a simpler model to try to deduce possible changes at the stem-cell level that might be responsible for the characteristics PCML.
