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Mutation signatures of pediatric acute myeloid leukemia and normal blood progenitors associated with differential patient outcomes.
Brandsma, Arianne M; Bertrums, Eline J M; van Roosmalen, Markus J; Hofman, Damon A; Oka, Rurika; Verheul, Mark; Manders, Freek; Ubels, Joske; Belderbos, Mirjam E; van Boxtel, Ruben.
Afiliación
  • Brandsma AM; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Bertrums EJM; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • van Roosmalen MJ; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Hofman DA; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Oka R; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Verheul M; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Manders F; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Ubels J; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • Belderbos ME; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands.
  • van Boxtel R; Princess Máxima Center for Pediatric Oncology and Oncode Institute, Utrecht, the Netherlands. R.vanBoxtel@prinsesmaximacentrum.nl.
Blood Cancer Discov ; 2(5): 484-499, 2021 09.
Article en En | MEDLINE | ID: mdl-34642666
Acquisition of oncogenic mutations with age is believed to be rate limiting for carcinogenesis. However, the incidence of leukemia in children is higher than in young adults. Here we compare somatic mutations across pediatric acute myeloid leukemia (pAML) patient-matched leukemic blasts and hematopoietic stem and progenitor cells (HSPCs), as well as HSPCs from age-matched healthy donors. HSPCs in the leukemic bone marrow have limited genetic relatedness and share few somatic mutations with the cell-of-origin of the malignant blasts, suggesting polyclonal hematopoiesis in pAML patients. Compared to normal HSPCs, a subset of pAML cases harbored more somatic mutations and a distinct composition of mutational process signatures. We hypothesize these cases might have arisen from a more committed progenitor. This subset had better outcomes than pAML cases with mutation burden comparable to age-matched healthy HSPCs. Our study provides insights into the etiology and patient stratification of pAML.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda Tipo de estudio: Risk_factors_studies Límite: Adult / Child / Humans Idioma: En Revista: Blood Cancer Discov Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda Tipo de estudio: Risk_factors_studies Límite: Adult / Child / Humans Idioma: En Revista: Blood Cancer Discov Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos