Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms. Cell Stem Cell. 2021 Feb 18.

Citation

Van Egeren D, Escabi J, Nguyen M, Liu S, Reilly CR, Patel S, Kamaz B, Kalyva M, DeAngelo DJ, Galinsky I, Wadleigh M, Winer ES, Luskin MR, Stone RM, Garcia JS, Hobbs GS, Camargo FD, Michor F, Mullally A, Cortes-Ciriano I, Hormoz S. 2021. Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms. Cell stem cell. 28(3):514-523.e9. Pubmed: 33621486 DOI:S1934-5909(21)00051-5

Abstract

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.

Related Faculty

Franziska Michor, Ph.D.

Michor Lab

Franziska Michor uses the tools of theoretical evolutionary biology, applied mathematics, statistics, and computational biology to address important questions in cancer research.