Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms

被引：148

作者：

Van Egeren, Debra ^{[1
,2
,3
]}

Escabi, Javier ^{[1
,2
,4
]}

Nguyen, Maximilian ^{[1
,2
]}

Liu, Shichen ^{[2
]}

Reilly, Christopher R. ^{[5
]}

Patel, Sachin ^{[3
]}

Kamaz, Baransel ^{[6
]}

Kalyva, Maria ^{[7
]}

DeAngelo, Daniel J. ^{[5
]}

Galinsky, Ilene ^{[5
]}

Wadleigh, Martha ^{[5
]}

Winer, Eric S. ^{[5
]}

Luskin, Marlise R. ^{[5
]}

Stone, Richard M. ^{[5
]}

Garcia, Jacqueline S. ^{[5
]}

Hobbs, Gabriela S. ^{[8
]}

Camargo, Fernando D. ^{[3
,9
]}

Michor, Franziska ^{[2
,9
,10
,11
,12
,13
]}

Mullally, Ann ^{[5
,6
,10
]}

Cortes-Ciriano, Isidro ^{[7
]}

Hormoz, Sahand ^{[1
,2
,10
]}

机构：

[1] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Data Sci, Boston, MA 02215 USA

[3] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[4] Harvard Grad Sch Arts & Sci, Res Scholar Initiat, Cambridge, MA 02138 USA

[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[6] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA

[7] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Hinxton, England

[8] Massachusetts Gen Hosp, Leukemia Ctr, Boston, MA 02114 USA

[9] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[10] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[11] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[12] Dana Farber Canc Inst, Ctr Canc Evolut, Boston, MA 02115 USA

[13] Ludwig Ctr Harvard, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2021年 / 28卷 / 03期

关键词：

V617F MUTATION OCCURS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; CLONAL HEMATOPOIESIS; SOMATIC MUTATIONS; RISK; DISORDERS; EVOLUTION; DISCOVERY; VARIANTS;

D O I：

10.1016/j.stem.2021.02.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Some cancers originate from a single mutation event in a single cell. Blood cancers known as myeloproliferative neoplasms (MPNs) are thought to originate when a driver mutation is acquired by a hematopoietic stem cell (HSC). However, when the mutation first occurs in individuals and how it affects the behavior of HSCs in their native context is not known. Here we quantified the effect of the JAK2-V617F mutation on the self-renewal and differentiation dynamics of HSCs in treatment-naive individuals with MPNs and reconstructed lineage histories of individual HSCs using somatic mutation patterns. We found that JAK2-V617F mutations occurred in a single HSC several decades before MPN diagnosis-at age 9 +/- 2 years in a 34-year-old individual and at age 19 +/- 3 years in a 63-year-old individual-and found that mutant HSCs have a selective advantage in both individuals. These results highlight the potential of harnessing somatic mutations to reconstruct cancer lineages.

引用

页码：514 / +

页数：19

共 63 条

[31] PHYLODYN: an R package for phylodynamic simulation and inference [J].