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The impact of an additional copy of chromosome 21 in B-cell precursor acute lymphoblastic leukemia.
Hormann, Femke M; Mooij, Eva J; van de Mheen, Marieke; Beverloo, H Berna; den Boer, Monique L; Boer, Judith M.
Afiliação
  • Hormann FM; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • Mooij EJ; Department of Pediatric Oncology/Hematology, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
  • van de Mheen M; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • Beverloo HB; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • den Boer ML; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Boer JM; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Genes Chromosomes Cancer ; 63(1): e23217, 2024 Jan.
Article em En | MEDLINE | ID: mdl-38087879
ABSTRACT
A common finding in pediatric B-cell precursor acute lymphoblastic leukemia (BCPALL) is that chromosome 21 is never lost and an extra chromosome 21 is often gained. This implies an important role for chromosome 21 in the pathobiology of BCPALL, emphasized by the increased risk of BCPALL in children with Down syndrome. However, model systems of chromosome 21 gain are lacking. We therefore developed a BCPALL cell line (Nalm-6, DUX4-rearranged) with an additional chromosome 21 by means of microcell-mediated chromosome transfer. FISH, PCR, multiplex ligation-dependent probe amplification, and whole exome sequencing showed that an additional chromosome 21 was successfully transferred to the recipient cells. Transcription of some but not all genes on chromosome 21 was increased, indicating tight transcriptional regulation. Nalm-6 cells with an additional chromosome 21 proliferated slightly slower compared with parental Nalm-6 and sensitivity to induction chemotherapeutics was mildly increased. The extra copy of chromosome 21 did not confer sensitivity to targeted signaling inhibitors. In conclusion, a BCPALL cell line with an additional human chromosome 21 was developed, validated, and subjected to functional studies, which showed a minor but potentially relevant effect in vitro. This cell line offers the possibility to study further the role of chromosome 21 in ALL.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Linfoma de Burkitt Limite: Child / Humans Idioma: En Revista: Genes Chromosomes Cancer Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Linfoma de Burkitt Limite: Child / Humans Idioma: En Revista: Genes Chromosomes Cancer Assunto da revista: BIOLOGIA MOLECULAR / NEOPLASIAS Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda