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2. Guideline for management of non-Down syndrome neonates with a myeloproliferative disease on behalf of the I-BFM AML Study Group and EWOG-MDS

Author

Bertrums, E. J. M., Zwaan, C. M., Hasegawa, D., de Haas, V., Reinhardt, D. N., Locatelli, Franco, de Moerloose, B., Dworzak, M., Buijs, A., Smisek, P., Kolenova, A., Pronk, C. J., Klusmann, J. -H., Carbone, A., Ferster, A., Antoniou, E., Meshinchi, S., Raimondi, S. C., Niemeyer, C. M., Hasle, H., van den Heuvel-Eibrink, M. M., Goemans, B. F., Locatelli F. (ORCID:0000-0002-7976-3654), Bertrums, E. J. M., Zwaan, C. M., Hasegawa, D., de Haas, V., Reinhardt, D. N., Locatelli, Franco, de Moerloose, B., Dworzak, M., Buijs, A., Smisek, P., Kolenova, A., Pronk, C. J., Klusmann, J. -H., Carbone, A., Ferster, A., Antoniou, E., Meshinchi, S., Raimondi, S. C., Niemeyer, C. M., Hasle, H., van den Heuvel-Eibrink, M. M., Goemans, B. F., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

no abstract

Published
2022

3. Increased risk of leukaemia in children with down syndrome:A somatic evolutionary view

Author

Hasaart, K. A.L., Bertrums, E. J.M., Manders, F., Goemans, B. F., van Boxtel, Ruben, Hasaart, K. A.L., Bertrums, E. J.M., Manders, F., Goemans, B. F., and van Boxtel, Ruben

Abstract

Children show a higher incidence of leukaemia compared with young adolescents, yet their cells are less damaged because of their young age. Children with Down syndrome (DS) have an even higher risk of developing leukaemia during the first years of life. The presence of a constitutive trisomy of chromosome 21 (T21) in DS acts as a genetic driver for leukaemia development, however, additional oncogenic mutations are required. Therefore, T21 provides the opportunity to better understand leukaemogenesis in children. Here, we describe the increased risk of leukaemia in DS during childhood from a somatic evolutionary view. According to this idea, cancer is caused by a variation in inheritable phenotypes within cell populations that are subjected to selective forces within the tissue context. We propose a model in which the increased risk of leukaemia in DS children derives from higher rates of mutation accumulation, already present during fetal development, which is further enhanced by changes in selection dynamics within the fetal liver niche. This model could possibly be used to understand the rate-limiting steps of leukaemogenesis early in life.

Published
2021

7. Antiviral treatment causes a unique mutational signature in cancers of transplantation recipients.

Author

de Kanter JK, Peci F, Bertrums E, Rosendahl Huber A, van Leeuwen A, van Roosmalen MJ, Manders F, Verheul M, Oka R, Brandsma AM, Bierings M, Belderbos M, and van Boxtel R

Subjects
Antiviral Agents therapeutic use, Humans, Transplant Recipients, Antiviral Agents adverse effects, Cytomegalovirus Infections drug therapy, Hematopoietic Stem Cell Transplantation, Mutation, Neoplasms genetics
Abstract

Genetic instability is a major concern for successful application of stem cells in regenerative medicine. However, the mutational consequences of the most applied stem cell therapy in humans, hematopoietic stem cell transplantation (HSCT), remain unknown. Here we characterized the mutation burden of hematopoietic stem and progenitor cells (HSPCs) of human HSCT recipients and their donors using whole-genome sequencing. We demonstrate that the majority of transplanted HSPCs did not display altered mutation accumulation. However, in some HSCT recipients, we identified multiple HSPCs with an increased mutation burden after transplantation. This increase could be attributed to a unique mutational signature caused by the antiviral drug ganciclovir. Using a machine learning approach, we detected this signature in cancer genomes of individuals who received HSCT or solid organ transplantation earlier in life. Antiviral treatment with nucleoside analogs can cause enhanced mutagenicity in transplant recipients, which may ultimately contribute to therapy-related carcinogenesis., Competing Interests: Declaration of interests A.R.H., A.v.L., and R.v.B. are named as inventors on a patent application filed resulting from this work., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2021
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