TY - JOUR
T1 - Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia
AU - Woodward, Eleanor L.
AU - Yang, Minjun
AU - Moura-Castro, Larissa H.
AU - van den Bos, Hilda
AU - Gunnarsson, Rebeqa
AU - Olsson-Arvidsson, Linda
AU - Spierings, Diana C.J.
AU - Castor, Anders
AU - Duployez, Nicolas
AU - Zaliova, Marketa
AU - Zuna, Jan
AU - Johansson, Bertil
AU - Foijer, Floris
AU - Paulsson, Kajsa
N1 - Funding Information:
The results published here are in part based upon data generated by the Therapeutically Applicable Research to Generate Effective Treatments ( https://ocg.cancer.gov/programs/target ) initiative, phs000218. Figures , , , and and Supplementary Figs. , , and were created with BioRender.com. This study was supported by grants from the Swedish Childhood Cancer Foundation, grant numbers PR2020-0033 (MY), TJ2020-0024 (MY), PR2018-0004 (BJ), and PR2018-0023 (KP); the Swedish Cancer Fund, grant numbers 20 0792 PjF (BJ) and 19-0252-Pj (KP); Governmental funding of clinical research within the National Health Service, grant number ALFSKANE-623431 (KP); the Swedish Research Council, grant numbers 2020-01164 (BJ) and 2020-00997 (KP); IngaBritt och Arne Lundbergs Forskningsstiftelse, grant number LU2019-0100 (KP), the Gunnar Nilsson Cancer Foundation (MY), the Royal Physiographic Society of Lund (EW), the Czech Health Research Council, grant number (NU20-07-00322)) (MZ)), the University Hospital Motol, grant number #00064203 (MZ, JZ), and Program EXCELES, grant number LX22NPO5102 (MZ, JZ).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-37356-5
DO - 10.1038/s41467-023-37356-5
M3 - Article
C2 - 36966135
AN - SCOPUS:85151001441
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
M1 - 1658
ER -