A progenitor cell origin of myeloid malignancies.

ABSTRACT: All cancers rely on cells that have properties of long-term self-renewal or "stemness" to maintain and propagate the tumor, but the cell of origin of most cancers is still unknown. Here, we design a stochastic mathematical model of hematopoietic stem and progenitor cells to study the evolutionary dynamics of cancer initiation. We consider different evolutionary pathways leading to cancer-initiating cells in JAK2V617F-positive myeloproliferative neoplasms (MPN): (i) the JAK2V617F mutation may arise in a stem cell; (ii) a progenitor cell may first acquire a mutation conferring self-renewal, followed by acquisition of the JAK2V617F mutation; (iii) the JAK2V617F mutation may first emerge in a progenitor cell, followed by a mutation conferring self-renewal; and (iv) a mutation conferring self-r

SUBMITTER: Haeno H 

PROVIDER: S-EPMC2757818 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature