Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia
Comparison of intratumor genetic heterogeneity in cancer at diagnosis and relapse suggests that chemotherapy induces bottleneck selection of subclonal genotypes. However, evolutionary events subsequent to chemotherapy could also explain changes in clonal dominance seen at relapse. We therefore investigated the mechanisms of selection in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) during induction chemotherapy where maximal cytoreduction occurs. To distinguish stochastic versus deterministic events, individual leukemias were transplanted into multiple xenografts and chemotherapy administered. Analyses of the immediate post-treatment leukemic residuum at single-cell resolution revealed that chemotherapy has little impact on genetic heterogeneity. Rather, it acts on extensive, previously unappreciated, transcriptional and epigenetic heterogeneity in BCP-ALL, dramatically reducing the spectrum of cell states represented, leaving a genetically polyclonal but phenotypically uniform population, with hallmark signatures relating to developmental stage, cell cycle and metabolism. Hence, canalization of the cell state accounts for a significant component of bottleneck selection during induction chemotherapy.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
Dataset ID | Description | Technology | Samples |
---|---|---|---|
EGAD00001006133 | NextSeq 500 | 74 | |
EGAD00001006134 | NextSeq 500 | 757 | |
EGAD00001006135 | NextSeq 500 | 285 | |
EGAD00001006136 | NextSeq 500 | 24 | |
EGAD00001006137 | NextSeq 500 | 539 | |
EGAD00001006138 | NextSeq 500 | 444 | |
EGAD00010001872 | EPIC arrays | 32 |
Publications | Citations |
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Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia.
Nat Cancer 2: 2021 835-852 |
18 |
Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL.
J Exp Med 221: 2024 e20230279 |
2 |