In Silico Investigation of the Role of Local and Global Inflammation-Driven Feedback in Myelopoiesis and Clonal Expansion

YusufJamilu Umar

Khalifa University, Abu Dhabi

"In Silico Investigation of the Role of Local and Global Inflammation-Driven Feedback in Myelopoiesis and Clonal Expansion"

Chronic inflammation disrupts hematopoietic homeostasis, causing pathological myelopoiesis and malignant clones that grow. The study uses a mathematical model with local (bone marrow) and global (peripheral inflammation) negative feedback mechanisms to examine how inflammation-driven regulations affect HSC self-renewal, progenitor dynamics, and differentiation. Healthy and malignant populations compete in the model, which examines system stability through feedback mechanisms. The results show that chronic inflammation can cause myelopoietic disorders by overproducing progenitor cells and disrupting lineage balance without global feedback regulation. Self-renewal feedback regulates stem cell proliferation to strengthen hematopoietic cells and mitigate chronic inflammation damages. Because excessive suppression can destabilize hematopoiesis, the model suggests tightly controlling negative feedback on progenitor cells. Mutations affecting global feedback can cause malignant clones, revealing how inflammation causes hematological malignancies like MDS and AML.
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