Cell stem cell · 2021
Reconstructing the Lineage Histories and Differentiation Trajectories of Individual Cancer Cells in Myeloproliferative Neoplasms.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Van Egeren Debra, Escabi Javier, Nguyen Maximilian, Liu Shichen, Reilly Christopher R, Patel Sachin, Kamaz Baransel, Kalyva Maria, DeAngelo Daniel J, Galinsky Ilene, Wadleigh Martha, Winer Eric S, Luskin Marlise R, Stone Richard M, Garcia Jacqueline S, Hobbs Gabriela S, Camargo Fernando D, Michor Franziska, Mullally Ann, Cortes-Ciriano Isidro, Hormoz Sahand
Аннотация
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.