Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

ACUTE MYELOID LEUKEMIA

Characterization of leukemia progression in the Cbfb-MYH11 knockin mice by single cell RNA sequencing

Leukemia volume 37, pages 1549–1553 (2023)Cite this article

Subjects

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Comparison of single cell transcriptome of bone marrow Kit+ progenitor/stem cells in wild-type mice and in conditional Cbfb-MYH11 knockin mice at pre-leukemic and leukemic stages.
Fig. 2: Identification of leukemia precursor cells and their candidate markers in the pre-leukemia mice.

Data availability

The datasets generated during and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) repository, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE219043.

References

  1. Liu P, Tarle SA, Hajra A, Claxton DF, Marlton P, Freedman M, et al. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science. 1993;261:1041–4.

    Article  CAS  PubMed  Google Scholar 

  2. Liu PP, Wijmenga C, Hajra A, Blake TB, Kelley CA, Adelstein RS, et al. Identification of the chimeric protein product of the CBFB-MYH11 fusion gene in inv(16) leukemia cells. Genes Chromosomes Cancer. 1996;16:77–87.

    Article  PubMed  Google Scholar 

  3. Castilla LH, Garrett L, Adya N, Orlic D, Dutra A, Anderson S, et al. The fusion gene Cbfb-MYH11 blocks myeloid differentiation and predisposes mice to acute myelomonocytic leukaemia. Nat Genet. 1999;23:144–6.

    Article  CAS  PubMed  Google Scholar 

  4. Kuo YH, Landrette SF, Heilman SA, Perrat PN, Garrett L, Liu PP, et al. Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia. Cancer Cell. 2006;9:57–68.

    Article  CAS  PubMed  Google Scholar 

  5. Zheng GX, Terry JM, Belgrader P, Ryvkin P, Bent ZW, Wilson R, et al. Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017;8:14049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, et al. Comprehensive integration of single-cell data. Cell. 2019;177:1888–1902.e1821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen H, Albergante L, Hsu JY, Lareau CA, Lo Bosco G, Guan J, et al. Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM. Nat Commun. 2019;10:1903.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Becht E, McInnes L, Healy J, Dutertre CA, Kwok IWH, Ng LG, et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat Biotechnol. 2018;37:38–44.

  9. Seita J, Sahoo D, Rossi DJ, Bhattacharya D, Serwold T, Inlay MA, et al. Gene Expression Commons: an open platform for absolute gene expression profiling. PLoS ONE. 2012;7:e40321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Nestorowa S, Hamey FK, Pijuan Sala B, Diamanti E, Shepherd M, Laurenti E, et al. A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood. 2016;128:e20–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Han X, Wang R, Zhou Y, Fei L, Sun H, Lai S, et al. Mapping the mouse cell atlas by microwell-seq. Cell. 2018;172:1091–1107.e1017.

    Article  CAS  PubMed  Google Scholar 

  12. Zhen T, Cao Y, Ren G, Zhao L, Hyde RK, Lopez G, et al. RUNX1 and CBFbeta-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development. Blood. 2020;136:2373–85.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hyde RK, Liu PP. RUNX1 repression-independent mechanisms of leukemogenesis by fusion genes CBFB-MYH11 and AML1-ETO (RUNX1-RUNX1T1). J Cell Biochem. 2010;110:1039–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Abdelbaset-Ismail A, Borkowska-Rzeszotek S, Kubis E, Bujko K, Brzezniakiewicz-Janus K, Bolkun L, et al. Activation of the complement cascade enhances motility of leukemic cells by downregulating expression of HO-1. Leukemia. 2017;31:446–58.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work was supported by the Intramural Research Programs of the National Human Genome Research Institute, National Institute on Deafness and Other Communication Disorders, and Natioal Cancer Institute, NIH. The authors would like to thank Zhi Liu and Jim Mullikin for preliminary STREAM testing, Erika Kwon, Erica Bresciani and Elisabeth Heuston for insightful discussion, as well as Luigi Alvarado (now at 10X Genomics) and the LaRochelle lab at NHLBI (NIH) for critical pilot drop-seq experiments that led to this study. This work used the computational resources of the NIH highperformance computing Biowulf cluster (https://hpc.nih.gov).

Author information

Author notes

  1. Michael Kelly

    Present address: Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Center for Cancer Research, Natioal Cancer Institute, NIH, Bethesda, MD, USA

Authors and Affiliations

  1. Oncogenesis and Development Section, Division of Intramural Research, National Human Genome Research Institute, NIH, Bethesda, MD, USA

    Jamie L. Diemer, Kai Yu, Tao Zhen, Guadalupe Lopez & Paul Liu

  2. Laboratory of Cochlear Development, Division of Intramural Research, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, USA

    Michael Kelly

  3. Flow Cytometry Core, Division of Intramural Research, National Human Genome Research Institute, NIH, Bethesda, MD, USA

    Stacie Anderson

Authors
  1. Jamie L. Diemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Zhen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stacie Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guadalupe Lopez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JD performed experiments, analyzed data, and wrote the manuscript, KY analyzed data and prepared several figures for the manuscript, MK assisted in sequencing, read mapping, and downsampling for sequencing depth normalization, TZ and GL prepared the conditional knockin mice used, and SA performed FACS isolation of the cells of interest.

Corresponding author

Correspondence to Paul Liu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diemer, J.L., Yu, K., Kelly, M. et al. Characterization of leukemia progression in the Cbfb-MYH11 knockin mice by single cell RNA sequencing. Leukemia 37, 1549–1553 (2023). https://doi.org/10.1038/s41375-023-01926-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-023-01926-9

Search

Advanced search

Quick links