Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2020 Nov 5;136(19):2235-2237.
doi: 10.1182/blood.2020008107.

Therapy-induced mutagenesis in relapsed ALL is supported by mutational signature analysis

Samuel W Brady  1 , Xiaotu Ma  1 , Bin-Bing S Zhou  2   3 , Ching-Hon Pui  4 , Jun J Yang  5 , Jinghui Zhang  1
Affiliations
Comment

Therapy-induced mutagenesis in relapsed ALL is supported by mutational signature analysis

Samuel W Brady et al. Blood. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Example showing the multistep acquisition of resistance in ALL. Cells are represented with mutations shown as small colored circles. At diagnosis (D), patient SJALL043859 had a subclonal mutation in SNRNP25 of uncertain significance in 10% of leukemic cells (10% cancer cell fraction or CCF), which increased to 87% at relapse (R). At relapse, an NT5C2 R367Q mutation was detected at 84% CCF within the SNRNP25 lineage, but was not found at diagnosis at 747× coverage, indicating that the NT5C2 variant descended from the SNRNP25 clone. The relapse sample also acquired the thiopurine signature (bottom), and the NT5C2 mutations had >50% probability of having been induced by thiopurines because it occurred at a thiopurine-preferred trinucleotide context. These findings are based on whole-genome sequencing and targeted deep sequencing (484 to 1284× coverage of the SNRNP25 and NT5C2 mutations).
See this image and copyright information in PMC

Comment on

References

    1. Gaynon PS, Orgel E, Ji L. Preexisting or therapy-induced mutations in relapsed acute lymphoblastic leukemia? Blood. 2020;136(19):2233-2235. - PubMed
    1. Li B, Brady SW, Ma X, et al. . Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia. Blood. 2020;135(1):41-55. - PMC - PubMed
    1. Morganella S, Alexandrov LB, Glodzik D, et al. . The topography of mutational processes in breast cancer genomes. Nat Commun. 2016;7(1):11383. - PMC - PubMed
    1. Dobson SM, García-Prat L, Vanner RJ, et al. . Relapse-fated latent diagnosis subclones in acute B lineage leukemia are drug tolerant and possess distinct metabolic programs. Cancer Discov. 2020;10(4):568-587. - PMC - PubMed
    1. Tzoneva G, Dieck CL, Oshima K, et al. . Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia. Nature. 2018;553(7689):511-514. - PMC - PubMed