A progenitor cell origin of myeloid malignancies
Hiroshi Haeno, Ross L. Levine, D. Gary Gilliland, Franziska Michor
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.
Myeloid Progenitor Cells
Haeno, H., Levine, R. L., Gilliland, D. G., & Michor, F. (2009). A progenitor cell origin of myeloid malignancies. Proceedings of the National Academy of Sciences of the United States of America, 106(39), 16616-16621. https://doi.org/10.1073/pnas.0908107106
A progenitor cell origin of myeloid malignancies. / Haeno, Hiroshi; Levine, Ross L.; Gilliland, D. Gary; Michor, Franziska.
Haeno, H, Levine, RL, Gilliland, DG & Michor, F 2009, 'A progenitor cell origin of myeloid malignancies', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 39, pp. 16616-16621. https://doi.org/10.1073/pnas.0908107106
Haeno H, Levine RL, Gilliland DG, Michor F. A progenitor cell origin of myeloid malignancies. Proceedings of the National Academy of Sciences of the United States of America. 2009 Sep 29;106(39):16616-16621. https://doi.org/10.1073/pnas.0908107106
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.
@article{6447b9645f104874b3a31a35c9180dc1,
title = "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-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.",
author = "Hiroshi Haeno and Levine, {Ross L.} and Gilliland, {D. Gary} and Franziska Michor",
T1 - A progenitor cell origin of myeloid malignancies
AU - Haeno, Hiroshi
AU - Levine, Ross L.
AU - Gilliland, D. Gary
AU - Michor, Franziska
N2 - 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.
AB - 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.