| 000 | 03006 am a22003493u 4500 | ||
|---|---|---|---|
| 042 | _adc | ||
| 100 | 1 | 0 |
_aBertrums, Eline J.M. _eauthor _91254 |
| 700 | 1 | 0 |
_aRosendahl Huber, Axel K.M. _eauthor _91255 |
| 700 | 1 | 0 |
_ade Kanter, Jurrian K. _eauthor _91256 |
| 700 | 1 | 0 |
_aBrandsma, Arianne M. _eauthor _91257 |
| 700 | 1 | 0 |
_avan Leeuwen, Anaïs J.C.N. _eauthor _91258 |
| 700 | 1 | 0 |
_aVerheul, Mark _eauthor _91259 |
| 700 | 1 | 0 |
_avan den Heuvel-Eibrink, Marry M. _eauthor _91260 |
| 700 | 1 | 0 |
_aOka, Rurika _eauthor _91261 |
| 700 | 1 | 0 |
_avan Roosmalen, Markus J. _eauthor _91262 |
| 700 | 1 | 0 |
_ade Groot-Kruseman, Hester A. _eauthor _91263 |
| 700 | 1 | 0 |
_aZwaan, C. Michel _eauthor _91264 |
| 700 | 1 | 0 |
_aGoemans, Bianca F. _eauthor _91265 |
| 700 | 1 | 0 |
_avan Boxtel, Ruben _eauthor _91266 |
| 245 | 0 | 0 | _aElevated Mutational Age in Blood of Children Treated for Cancer Contributes to Therapy-Related Myeloid Neoplasms |
| 260 |
_bAmerican Association for Cancer Research, _c2022-08-05. |
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| 500 | _a/pmc/articles/PMC7613255/ | ||
| 500 | _a/pubmed/35678530 | ||
| 520 | _aChildhood cancer survivors are confronted with various chronic health conditions like therapy-related malignancies. However, it is unclear how exposure to chemotherapy contributes to the mutation burden and clonal composition of healthy tissues early in life. Here, we studied mutation accumulation in hematopoietic stem and progenitor cells (HSPC) before and after cancer treatment of 24 children. Of these children, 19 developed therapy-related myeloid neoplasms (t-MN). Posttreatment HSPCs had an average mutation burden increase comparable to what treatment-naïve cells accumulate during 16 years of life, with excesses up to 80 years. In most children, these additional mutations were induced by clock-like processes, which are also active during healthy aging. Other patients harbored mutations that could be directly attributed to treatments like platinum-based drugs and thiopurines. Using phylogenetic inference, we demonstrate that most t-MN in children originate after the start of treatment and that leukemic clones become dominant during or directly after chemotherapy exposure. SIGNIFICANCE: Our study shows that chemotherapy increases the mutation burden of normal blood cells in cancer survivors. Only few drugs damage the DNA directly, whereas in most patients, chemotherapy-induced mutations are caused by processes similar to those present during normal aging. This article is highlighted in the In This Issue feature, p. 1825 | ||
| 540 | _a©2022 The Authors; Published by the American Association for Cancer Research | ||
| 540 | _ahttps://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. | ||
| 546 | _aen | ||
| 690 |
_aResearch Briefs _91267 |
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| 655 | 7 |
_aText _2local |
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| 786 | 0 | _nCancer Discov | |
| 856 | 4 | 1 |
_uhttp://dx.doi.org/10.1158/2159-8290.CD-22-0120 _zConnect to this object online. |
| 999 |
_c294 _d294 |
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