Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia.
Eleanor L WoodwardMinjun YangLarissa Helena Moura-CastroHilda van den BosRebeqa GunnarssonLinda Olsson-ArvidssonDiana Carolina Johanna SpieringsAnders CastorNicolas DuployezMarketa ZaliovaJan ZunaBertil JohanssonFloris FoijerKajsa PaulssonPublished in: Nature communications (2023)
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.
Keyphrases
- copy number
- single cell
- mitochondrial dna
- acute lymphoblastic leukemia
- genome wide
- bone marrow
- rna seq
- dna methylation
- induced apoptosis
- high throughput
- liver failure
- early life
- acute myeloid leukemia
- stem cells
- respiratory failure
- cell therapy
- big data
- machine learning
- hepatitis b virus
- aortic dissection
- molecular docking
- intensive care unit
- gene expression
- artificial intelligence
- cell death
- drug induced