Mathematical Modelling as a Proof of Concept for MPNs as a Human Inflammation Model for Cancer Development

<p><b>Left:</b> Typical development in stem cells (top panel A) and mature cells (bottom panel B). Healthy hematopoietic cells (full blue curves) dominate in the early phase where the number of malignant cells (stipulated red curves) are few. The total number of cells is also shown (dotted green curves). When a stem cell mutates without repairing mechanisms, a slowly increasing exponential growth starts. At a certain stage, the malignant cells become dominant, and the healthy hematopoietic cells begin to show a visible decline. Finally, the composition between the cell types results in a takeover by the malignant cells, leading to an exponential decline in hematopoietic cells and ultimately their extinction. The development is driven by an approximately exponential increase in the MPN stem cells, and the development is closely followed by the mature MPN cells. <b>Right:</b> B)The corresponding allele burden (7%, 33% and 67% corresponding to ET, PV, and PMF, respectively) defined as the ratio of MPN mature cells to the total number of mature cells.</p