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

Eleanor L. Woodward, Minjun Yang, Larissa H. Moura-Castro, Hilda Bos, Rebeqa Gunnarsson, Linda Olsson-Arvidsson, Diana C. J. Spierings, Anders Castor, Nicolas Duployez, Marketa Zaliova, Jan Zuna, Bertil Johansson, Floris Foijer and Kajsa Paulsson ()
Additional contact information
Eleanor L. Woodward: Lund University
Minjun Yang: Lund University
Larissa H. Moura-Castro: Lund University
Hilda Bos: University of Groningen, University Medical Center Groningen
Rebeqa Gunnarsson: Lund University
Linda Olsson-Arvidsson: Lund University
Diana C. J. Spierings: University of Groningen, University Medical Center Groningen
Anders Castor: Lund University
Nicolas Duployez: Centre Hospitalier Universitaire (CHU) Lille
Marketa Zaliova: Charles University/University Hospital Motol
Jan Zuna: Charles University/University Hospital Motol
Bertil Johansson: Lund University
Floris Foijer: University of Groningen, University Medical Center Groningen
Kajsa Paulsson: Lund University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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 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.

Date: 2023
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DOI: 10.1038/s41467-023-37356-5

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