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Merlevede J, Droin N, Qin T, Meldi K, Yoshida K, Morabito M, et al. Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nat Commun. 2016;7:10767.
Mason CC, Khorashad JS, Tantravahi SK, Kelley TW, Zabriskie MS, Yan D, et al. Age-related mutations and chronic myelomonocytic leukemia. Leukemia. 2016;30:906–13.
Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478:64–9.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.
Meldi K, Qin T, Buchi F, Droin N, Sotzen J, Micol JB, et al. Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia. J Clin Invest. 2015;125:1857–72.
Bejar R, Lord A, Stevenson K, Bar-Natan M, Perez-Ladaga A, Zaneveld J, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124:2705–12.
Tantravahi SK, Szankasi P, Khorashad JS, Dao K-H, Kovacsovics T, Kelley TW, et al. A phase II study of the efficacy, safety, and determinants of response to 5-azacitidine (Vidaza®) in patients with chronic myelomonocytic leukemia. Leuk Lymphoma. 2016;57:2441–4. 2016/10/02
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502:333–9.
Schuetz JM, Johnson NA, Morin RD, Scott DW, Tan K, Ben-Nierah S, et al. BCL2 mutations in diffuse large B-cell lymphoma. Leukemia. 2012;26:1383–90.
Qiao Y, Quinlan AR, Jazaeri AA, Verhaak RG, Wheeler DA, Marth GT. SubcloneSeeker: a computational framework for reconstructing tumor clone structure for cancer variant interpretation and prioritization. Genome Biol. 2014;15:443.
Patel BJ, Przychodzen B, Thota S, Radivoyevitch T, Visconte V, Kuzmanovic T, et al. Genomic determinants of chronic myelomonocytic leukemia. Leukemia. 2017;31:2815–23.
Dunbar AJ, Gondek LP, O’Keefe CL, Makishima H, Rataul MS, Szpurka H, et al. 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res. 2008;68:10349–57.
Grand FH, Hidalgo-Curtis CE, Ernst T, Zoi K, Zoi C, McGuire C, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood. 2009;113:6182–92.
Grun D, van Oudenaarden A. Design and analysis of single-cell sequencing experiments. Cell. 2015;163:799–810.
Brady SW, McQuerry JA, Qiao Y, Piccolo SR, Shrestha G, Jenkins DF, et al. Combating subclonal evolution of resistant cancer phenotypes. Nat Commun. 2017;8:1231.
This work was supported by a Leukemia and Lymphoma Society (LLS) Translational Research Program Award (6086-12) (M.W.D.) and an LLS Specialized Center of Research Program Award (GCNCR0314A-UTAH) (M.W.D.). This work was also supported by the National Institutes of Health (NIH) National Cancer Institute grant R01CA178397 (M.W.D. and T.O.), the V Foundation for Cancer Research grant (M.W.D. and T.O.) and by U01HG006513 (G.T.M.). J.S.K. was a special fellow of the LLS and was supported by a Translational Research Training in Hematology Award from the American Society of Hematology (ASH). H.T. was a visiting scholar from Singapore, and was supported by the Research Training Fellowship from National Medical Research Council of Singapore. We thank Brian K. Dalley, director of High-Throughput Genomics Core Facility, and James Marvin, director of Flow Cytometry Core Facility, at the University of Utah for their assistance with the experiments. The University of Utah Flow Cytometry Facility was supported by the National Cancer Institute through award 5P30CA042014-24 and the National Center for Research Resources of the National Institutes of Health under award 1S10RR026802-01. The University of Utah High-Throughput Genomics Core Facility was supported by Award Number P30CA042014 from the National Cancer Institute.
H.T., Y.Q., and M.W.D. conceived the project and analyzed data. H.T., T.O., and M.W.D. wrote the manuscript. Y.Q., X.H., and G.T.M. designed the software and analyzed data. H.T., D.Y., and J.S.K. prepared the samples and performed experiments. M.W.D. and T.J.K. provided clinical information and research materials. A.D.P. and T.O. critically reviewed the manuscript.
Conflict of interest
M.W.D. is on the advisory board and is a consultant for Incyte, Novartis and Pfizer, and serves on the advisory board for Ariad, Blueprint, and Galena BioPharma. His laboratory receives research funding from Novartis and Pfizer.
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Than, H., Qiao, Y., Huang, X. et al. Ongoing clonal evolution in chronic myelomonocytic leukemia on hypomethylating agents: a computational perspective. Leukemia 32, 2049–2054 (2018). https://doi.org/10.1038/s41375-018-0050-z