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Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia

Woodward, Eleanor L LU ; Yang, Minjun LU ; Moura-Castro, Larissa H LU orcid ; van den Bos, Hilda ; Gunnarsson, Rebeqa LU ; Olsson-Arvidsson, Linda LU ; Spierings, Diana C J ; Castor, Anders LU orcid ; Duployez, Nicolas and Zaliova, Marketa , et al. (2023) In Nature Communications 14.
Abstract

High hyperdiploid acute lymphoblastic leukemia (HeH ALL), one of the most common childhood malignancies, is driven by nonrandom aneuploidy (abnormal chromosome numbers) mainly comprising chromosomal gains. In this study, we investigate how aneuploidy in HeH ALL arises. Single cell whole genome sequencing of 2847 cells from nine primary cases and one normal bone marrow reveals that HeH ALL generally display low chromosomal heterogeneity, indicating that they are not characterized by chromosomal instability and showing that aneuploidy-driven malignancies are not necessarily chromosomally heterogeneous. Furthermore, most chromosomal gains are present in all leukemic cells, suggesting that they arose early during leukemogenesis. Copy number... (More)

High hyperdiploid acute lymphoblastic leukemia (HeH ALL), one of the most common childhood malignancies, is driven by nonrandom aneuploidy (abnormal chromosome numbers) mainly comprising chromosomal gains. In this study, we investigate how aneuploidy in HeH ALL arises. Single cell whole genome sequencing of 2847 cells from nine primary cases and one normal bone marrow reveals that HeH ALL generally display low chromosomal heterogeneity, indicating that they are not characterized by chromosomal instability and showing that aneuploidy-driven malignancies are not necessarily chromosomally heterogeneous. Furthermore, most chromosomal gains are present in all leukemic cells, suggesting that they arose early during leukemogenesis. Copy number data from 577 primary cases reveals selective pressures that were used for in silico modeling of aneuploidy development. This shows that the aneuploidy in HeH ALL likely arises by an initial tripolar mitosis in a diploid cell followed by clonal evolution, in line with a punctuated evolution model.

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Contribution to journal
publication status
published
subject
keywords
Humans, Aneuploidy, Chromosome Aberrations, Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics, Diploidy, Chromosomal Instability
in
Nature Communications
volume
14
article number
1658
publisher
Nature Publishing Group
external identifiers
  • scopus:85151001441
  • pmid:36966135
ISSN
2041-1723
DOI
10.1038/s41467-023-37356-5
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
08915c58-37e3-46df-99d0-a2234d37891c
date added to LUP
2023-05-02 15:50:35
date last changed
2025-02-10 04:22:40
@article{08915c58-37e3-46df-99d0-a2234d37891c,
  abstract     = {{<p>High hyperdiploid acute lymphoblastic leukemia (HeH ALL), one of the most common childhood malignancies, is driven by nonrandom aneuploidy (abnormal chromosome numbers) mainly comprising chromosomal gains. In this study, we investigate how aneuploidy in HeH ALL arises. Single cell whole genome sequencing of 2847 cells from nine primary cases and one normal bone marrow reveals that HeH ALL generally display low chromosomal heterogeneity, indicating that they are not characterized by chromosomal instability and showing that aneuploidy-driven malignancies are not necessarily chromosomally heterogeneous. Furthermore, most chromosomal gains are present in all leukemic cells, suggesting that they arose early during leukemogenesis. Copy number data from 577 primary cases reveals selective pressures that were used for in silico modeling of aneuploidy development. This shows that the aneuploidy in HeH ALL likely arises by an initial tripolar mitosis in a diploid cell followed by clonal evolution, in line with a punctuated evolution model.</p>}},
  author       = {{Woodward, Eleanor L and Yang, Minjun and Moura-Castro, Larissa H and van den Bos, Hilda and Gunnarsson, Rebeqa and Olsson-Arvidsson, Linda and Spierings, Diana C J and Castor, Anders and Duployez, Nicolas and Zaliova, Marketa and Zuna, Jan and Johansson, Bertil and Foijer, Floris and Paulsson, Kajsa}},
  issn         = {{2041-1723}},
  keywords     = {{Humans; Aneuploidy; Chromosome Aberrations; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics; Diploidy; Chromosomal Instability}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia}},
  url          = {{http://dx.doi.org/10.1038/s41467-023-37356-5}},
  doi          = {{10.1038/s41467-023-37356-5}},
  volume       = {{14}},
  year         = {{2023}},
}