227 Copyright © 2013, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited. Chapter 15 DOI: 10.4018/978-1-4666-2657-7.ch015 George I. Lambrou University of Athens, Greece Apostolos Zaravinos University of Athens, Greece Maria Adamaki University of Athens, Greece Spiros Vlahopoulos University of Athens, Greece Systems Modeling of Proliferation Mechanisms in Childhood Acute Lymphoblastic Leukemia ABSTRACT Acute Lymphoblastic Leukemia (ALL) is the most common neoplasm in children, but the mechanisms underlying leukemogenesis are poorly understood, despite the existence of several theories regarding the mechanics of leukemic cell proliferation. However, with the advent of new biological principles, it appears that a systems approach could be used in an effective search of global patterns in biological systems, so as to be able to model the phenomenon of proliferation and gain a better understanding of how cells may progress from a healthy to a diseased state. This chapter reviews the current knowledge on proliferation dynamics, along with a discussion of the several existing theories on leukemogenesis and their comparison with the theories governing general oncogenesis. Furthermore, the authors pres- ent some “in-house” experimental data that support the view that it is possible to model leukemic cell proliferation and explain how this has been performed in in vitro experiments.