Dynamics of clonal evolution in myelodysplastic syndromes

Hideki Makishima; Tetsuichi Yoshizato; Kenichi Yoshida; Mikkael A. Sekeres; Tomas Radivoyevitch; Hiromichi Suzuki; Bartlomie J. Przychodzen; Yasunobu Nagata; Manja Meggendorfer; Masashi Sanada; Yusuke Okuno; Cassandra Hirsch; Teodora Kuzmanovic; Yusuke Sato; Aiko Sato-Otsubo; Thomas Laframboise; Naoko Hosono; Yuichi Shiraishi; Kenichi Chiba; Claudia Haferlach; Wolfgang Kern; Hiroko Tanaka; Yusuke Shiozawa; Inés Gómez-Seguí; Holleh D. Husseinzadeh; Swapna Thota; Kathryn M. Guinta; Brittney Dienes; Tsuyoshi Nakamaki; Shuichi Miyawaki; Yogen Saunthararajah; Shigeru Chiba; Satoru Miyano; Lee Yung Shih; Torsten Haferlach; Seishi Ogawa; Jaroslaw P. MacIejewski

doi:10.1038/ng.3742

Dynamics of clonal evolution in myelodysplastic syndromes

Hideki Makishima, Tetsuichi Yoshizato, Kenichi Yoshida, Mikkael A. Sekeres, Tomas Radivoyevitch, Hiromichi Suzuki, Bartlomie J. Przychodzen, Yasunobu Nagata, Manja Meggendorfer, Masashi Sanada, Yusuke Okuno, Cassandra Hirsch, Teodora Kuzmanovic, Yusuke Sato, Aiko Sato-Otsubo, Thomas Laframboise, Naoko Hosono, Yuichi Shiraishi, Kenichi Chiba, Claudia HaferlachWolfgang Kern, Hiroko Tanaka, Yusuke Shiozawa, Inés Gómez-Seguí, Holleh D. Husseinzadeh, Swapna Thota, Kathryn M. Guinta, Brittney Dienes, Tsuyoshi Nakamaki, Shuichi Miyawaki, Yogen Saunthararajah, Shigeru Chiba, Satoru Miyano, Lee Yung Shih, Torsten Haferlach, Seishi Ogawa, Jaroslaw P. MacIejewski^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

344 Scopus citations

Abstract

To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.

Original language	English
Pages (from-to)	204-212
Number of pages	9
Journal	Nature Genetics
Volume	49
Issue number	2
DOIs	https://doi.org/10.1038/ng.3742
State	Published - 31 01 2017

Bibliographical note

Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature.

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Makishima, H., Yoshizato, T., Yoshida, K., Sekeres, M. A., Radivoyevitch, T., Suzuki, H., Przychodzen, B. J., Nagata, Y., Meggendorfer, M., Sanada, M., Okuno, Y., Hirsch, C., Kuzmanovic, T., Sato, Y., Sato-Otsubo, A., Laframboise, T., Hosono, N., Shiraishi, Y., Chiba, K., ... MacIejewski, J. P. (2017). Dynamics of clonal evolution in myelodysplastic syndromes. Nature Genetics, 49(2), 204-212. https://doi.org/10.1038/ng.3742

@article{3f0b67d3d49a4eeb96c6d40fbdc543a1,

title = "Dynamics of clonal evolution in myelodysplastic syndromes",

abstract = "To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.",

author = "Hideki Makishima and Tetsuichi Yoshizato and Kenichi Yoshida and Sekeres, \{Mikkael A.\} and Tomas Radivoyevitch and Hiromichi Suzuki and Przychodzen, \{Bartlomie J.\} and Yasunobu Nagata and Manja Meggendorfer and Masashi Sanada and Yusuke Okuno and Cassandra Hirsch and Teodora Kuzmanovic and Yusuke Sato and Aiko Sato-Otsubo and Thomas Laframboise and Naoko Hosono and Yuichi Shiraishi and Kenichi Chiba and Claudia Haferlach and Wolfgang Kern and Hiroko Tanaka and Yusuke Shiozawa and In{\'e}s G{\'o}mez-Segu{\'i} and Husseinzadeh, \{Holleh D.\} and Swapna Thota and Guinta, \{Kathryn M.\} and Brittney Dienes and Tsuyoshi Nakamaki and Shuichi Miyawaki and Yogen Saunthararajah and Shigeru Chiba and Satoru Miyano and Shih, \{Lee Yung\} and Torsten Haferlach and Seishi Ogawa and MacIejewski, \{Jaroslaw P.\}",

note = "Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature.",

year = "2017",

month = jan,

day = "31",

doi = "10.1038/ng.3742",

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volume = "49",

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Makishima, H, Yoshizato, T, Yoshida, K, Sekeres, MA, Radivoyevitch, T, Suzuki, H, Przychodzen, BJ, Nagata, Y, Meggendorfer, M, Sanada, M, Okuno, Y, Hirsch, C, Kuzmanovic, T, Sato, Y, Sato-Otsubo, A, Laframboise, T, Hosono, N, Shiraishi, Y, Chiba, K, Haferlach, C, Kern, W, Tanaka, H, Shiozawa, Y, Gómez-Seguí, I, Husseinzadeh, HD, Thota, S, Guinta, KM, Dienes, B, Nakamaki, T, Miyawaki, S, Saunthararajah, Y, Chiba, S, Miyano, S, Shih, LY, Haferlach, T, Ogawa, S & MacIejewski, JP 2017, 'Dynamics of clonal evolution in myelodysplastic syndromes', Nature Genetics, vol. 49, no. 2, pp. 204-212. https://doi.org/10.1038/ng.3742

TY - JOUR

T1 - Dynamics of clonal evolution in myelodysplastic syndromes

AU - Makishima, Hideki

AU - Yoshizato, Tetsuichi

AU - Yoshida, Kenichi

AU - Sekeres, Mikkael A.

AU - Radivoyevitch, Tomas

AU - Suzuki, Hiromichi

AU - Przychodzen, Bartlomie J.

AU - Nagata, Yasunobu

AU - Meggendorfer, Manja

AU - Sanada, Masashi

AU - Okuno, Yusuke

AU - Hirsch, Cassandra

AU - Kuzmanovic, Teodora

AU - Sato, Yusuke

AU - Sato-Otsubo, Aiko

AU - Laframboise, Thomas

AU - Hosono, Naoko

AU - Shiraishi, Yuichi

AU - Chiba, Kenichi

AU - Haferlach, Claudia

AU - Kern, Wolfgang

AU - Tanaka, Hiroko

AU - Shiozawa, Yusuke

AU - Gómez-Seguí, Inés

AU - Husseinzadeh, Holleh D.

AU - Thota, Swapna

AU - Guinta, Kathryn M.

AU - Dienes, Brittney

AU - Nakamaki, Tsuyoshi

AU - Miyawaki, Shuichi

AU - Saunthararajah, Yogen

AU - Chiba, Shigeru

AU - Miyano, Satoru

AU - Shih, Lee Yung

AU - Haferlach, Torsten

AU - Ogawa, Seishi

AU - MacIejewski, Jaroslaw P.

PY - 2017/1/31

Y1 - 2017/1/31

N2 - To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.

AB - To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones. Enriched in secondary acute myeloid leukemia (sAML; in comparison to high-risk MDS), FLT3, PTPN11, WT1, IDH1, NPM1, IDH2 and NRAS mutations (type 1) tended to be newly acquired, and were associated with faster sAML progression and a shorter overall survival time. Significantly enriched in high-risk MDS (in comparison to low-risk MDS), TP53, GATA2, KRAS, RUNX1, STAG2, ASXL1, ZRSR2 and TET2 mutations (type 2) had a weaker impact on sAML progression and overall survival than type-1 mutations. The distinct roles of type-1 and type-2 mutations suggest their potential utility in disease monitoring.

UR - https://www.scopus.com/pages/publications/85006365447

U2 - 10.1038/ng.3742

DO - 10.1038/ng.3742

M3 - 文章

C2 - 27992414

AN - SCOPUS:85006365447

SN - 1061-4036

VL - 49

SP - 204

EP - 212

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Dynamics of clonal evolution in myelodysplastic syndromes

Abstract

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