Kimmel, MarekCorey, Seth2013-06-282013-06-282013Kimmel, Marek and Corey, Seth. "Stochastic hypothesis of transition from inborn neutropenia to AML: interactions of cell population dynamics and population genetics." <i>Frontiers in Oncology,</i> 3, (2013) Frontiers Media: http://dx.doi.org/10.3389/fonc.2013.00089.https://hdl.handle.net/1911/71486We present a stochastic model of driver mutations in the transition from severe congenital neutropenia to myelodysplastic syndrome to acute myeloid leukemia (AML). The model has the form of a multitype branching process. We derive equations for the distributions of the times to consecutive driver mutations and set up simulations involving a range of hypotheses regarding acceleration of the mutation rates in successive mutant clones. Our model reproduces the clinical distribution of times at diagnosis of secondary AML. Surprisingly, within the framework of our assumptions, stochasticity of the mutation process is incapable of explaining the spread of times at diagnosis of AML in this case; it is necessary to additionally assume a wide spread of proliferative parameters among disease cases. This finding is unexpected but generally consistent with the wide heterogeneity of characteristics of human cancers.engThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.Journal articlesevere congenital neutropeniamyelodysplastic syndromeacute myeloid leukemiabranching processdriver mutationsclonal evolutionhttp://dx.doi.org/10.3389/fonc.2013.00089