In this study, we combine a cell-based computational model of the thymus with complementary in vivo experiments in medaka (Oryzias latipes) to systematically analyze the impact of 12 cell-autonomous and non-autonomous factors, individually and in combination, on the proliferation of normal and malignant thymocytes carrying interleukin-7 receptor (IL7R) gain-of-function mutations or elevated IL7R levels, as observed in T-ALL patients. Here, IL7R is linked to acute lymphoblastic leukemia.