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| Item Type: | Article |
|---|---|
| Title: | Single-cell analysis based dissection of clonality in myelofibrosis |
| Creators Name: | Mylonas, E. and Yoshida, K. and Frick, M. and Hoyer, K. and Christen, F. and Kaeda, J. and Obenaus, M. and Noerenberg, D. and Hennch, C. and Chan, W. and Ochi, Y. and Shiraishi, Y. and Shiozawa, Y. and Zenz, T. and Oakes, C.C. and Sawitzki, B. and Schwarz, M. and Bullinger, L. and le Coutre, P. and Rose-Zerilli, M.J.J. and Ogawa, S. and Damm, F. |
| Abstract: | Cancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events. |
| Keywords: | Clonal Evolution, Exome, Follow-Up Studies, Genetic Heterogeneity, Mutation, Oncogene Protein p21(ras), Primary Myelofibrosis, Prospective Studies, Single-Cell Analysis, Stem Cells |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 11 |
| Number: | 1 |
| Page Range: | 73 |
| Date: | 7 January 2020 |
| Official Publication: | https://doi.org/10.1038/s41467-019-13892-x |
| PubMed: | View item in PubMed |
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