Modeling clonal dominance in myeloproliferative disorders. (A) The stem cell microenvironment is a complex cellular network consisting of many cell types, including macrophages, T cells, osteoblasts, endothelial cells, and fibroblasts. These cells modulate stem cell behavior through direct cell-cell interactions and through the secretion of cytokines. In addition, cytokines, chemokines, and other substances transit the marrow sinuses and may concentrate in certain regions (by adherence to extracellular matrix). (B) Depicted is a 2-compartment model for hematopoiesis. The first compartment represents a quiescent pool, or reserve, of stem cells. A cell in the reserve may self-replicate (with intensity, or conditional probability per unit time, λ), die (with intensity α), or initiate differentiation (with intensity ν) by entering the contributing compartment (compartment 2), at which stage cells actively divide and differentiate to contribute progenitor cells (and then mature cells) to marrow (and blood). A clone departing from the contributing compartment is considered to be “exhausted” (which occurs with intensity μ).