A progenitor cell origin of myeloid malignancies

Hiroshi Haeno, Ross L. Levine, D. Gary Gilliland, Franziska Michor

Research output: Contribution to journalArticle

37 Citations (Scopus)

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-renewal to progenitors may arise in the stem cell population without causing a change in the stem cell's phenotype, followed by the JAK2V617F mutation emerging in a progenitor cell. We find mathematical evidence that a progenitor is the most likely cell of origin of JAK2V617F-mutant MPN. These results may also have relevance to other tumor types arising in tissues that are organized as a differentiation hierarchy.

Original languageEnglish
Pages (from-to)16616-16621
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number39
DOIs
Publication statusPublished - Sep 29 2009

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Myeloid Progenitor Cells
Stem Cells
Mutation
Neoplasms
Hematopoietic Stem Cells
Theoretical Models
Phenotype

All Science Journal Classification (ASJC) codes

  • General

Cite this

A progenitor cell origin of myeloid malignancies. / Haeno, Hiroshi; Levine, Ross L.; Gilliland, D. Gary; Michor, Franziska.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 39, 29.09.2009, p. 16616-16621.

Research output: Contribution to journalArticle

Haeno, Hiroshi ; Levine, Ross L. ; Gilliland, D. Gary ; Michor, Franziska. / A progenitor cell origin of myeloid malignancies. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 39. pp. 16616-16621.
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