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.

  • Letter
  • Published:

Acute myeloid leukemia

Archived bone marrow smears are an excellent source for NGS-based mutation detection in acute myeloid leukemia

Leukemia volume 34, pages 2220–2224 (2020)Cite this article

Subjects

Acute myeloid leukemia (AML) is a heterogeneous disease as illustrated by the enormous diversity in numbers, types and often patient-specific molecular alterations. The current AML prognostic paradigm classifying patient into three 2017ELN risk groups relies solely on cytogenetic and molecular findings at baseline [1]. Besides the established clinically relevant aberrations, numerous acquired mutations have been revealed in AML [2, 3]. The clinical relevance of many of these somatic mutations is currently unknown because sufficient materials of AML patients carrying these less frequent mutations are lacking. Similarly, studies on the evolution of AML between initial diagnosis and relapse and minimal residual disease (MRD) detection have been hampered by inaccurate sampling during the course of the disease. Here we explored the feasibility of using archived May-Grünwald Giemsa stained bone marrow (MGG-stained BM) slides for next-generation sequencing (NGS)-based mutation detection. MGG-stained BM slides, taken at all clinically relevant time points, are widely available in contemporary biobanks. This study shows that archived MGG-stained BM slides are an excellent source for retrospective molecular analyses of AML, which could certainly be valuable for similar analyses of other hematologic malignancies.

We did notice variations in variant allele frequencies (VAFs) in few AML samples. A consistently lower VAF in MGG-stained BM DNA as compared to FPBM DNA could be the result of a variety of cells present on MGG-stained BM slides, such as unmutated stromal or differentiated cells. Ficoll purification enriches for mononuclear cells, which would result in increased percentages of blast cells and higher VAFs in FPBM DNA. In few instances VAFs were higher in MGG-stained BM DNA. These differences were mostly seen in genes known to be associated with clonal hematopoiesis, i.e., DNMT3A and TET2 [4, 5]. In these cases more differentiated cells carrying these mutations may have been lost during Ficoll purification resulting in decreased VAFs in the FPBM samples.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Mutation detection by targeted NGS on DNA isolated from MGG-stained BM slides and FPBM samples.
Fig. 2: Longitudinal mutation detection by targeted NGS on DNA derived from MGG-stained BM slides.

References

  1. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–47.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson AG, et al. Genomic and epigenomic landscapes of Adult De Novo Acute myeloid leukemia. N Engl J Med. 2013;368:2059–74.

    Article  PubMed  Google Scholar 

  3. Grimwade D, Ivey A, Huntly BJP. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2016;127:29–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377:111–21.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Shlush LI. Age-related clonal hematopoiesis. Blood. 2018;131:496–504.

    Article  CAS  PubMed  Google Scholar 

  6. Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481:506–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yilmaz M, Wang F, Loghavi S, Bueso-Ramos C, Gumbs C, Little L, et al. Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia? Blood Cancer J. 2019;9:7.

  8. Xu N, Ding L, Yin C, Zhou X, Li L, Li Y, et al. A report on the co-occurrence of JAK2V617F and CALR mutations in myeloproliferative neoplasm patients. Ann Hematol. 2015;94:865–7.

    Article  PubMed  Google Scholar 

  9. Rashid M, Ahmed RZ, Ahmed S, Nadeem M, Ahmed N, Shamsi TS. Coexisting JAK2V617F and CALR Exon 9 mutation in essential thrombocythemia. Indian J Hematol Blood Transfus. 2016;32:112–6.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank all the participating centers of the Dutch–Belgian Cooperative Trial Group for Hematology–Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK), where the clinical trials that formed the basis for this study were conducted; H. Berna Beverloo for performing cytogenetic analyses; Eric Bindels for performing next-generation sequencing, Remco Hoogenboezem for assisting with bioinformatics, and Egied Simons for assisting with preparation of the figures.

Author information

Authors and Affiliations

  1. National Genetic Center, Ministry of Health, Muscat, Sultanate of Oman

    Adil S. A. Al Hinai

  2. Erasmus University Medical Center, Rotterdam, the Netherlands

    Adil S. A. Al Hinai, Tim Grob, François G. Kavelaars, Melissa Rijken, Annelieke Zeilemaker, Claudia A. J. Erpelinck-Verschueren, Kirsten J. Gussinklo, Mathijs A. Sanders, Kirsten van Lom & Peter J. M. Valk

Authors
  1. Adil S. A. Al Hinai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tim Grob
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. François G. Kavelaars
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Melissa Rijken
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annelieke Zeilemaker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Claudia A. J. Erpelinck-Verschueren
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kirsten J. Gussinklo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mathijs A. Sanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kirsten van Lom
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peter J. M. Valk
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ASAAH: performed research, analyzed data and wrote the paper; TG, FGK, MR, AZ, CAJ, KJG, MAS, and KvL: performed research, and analyzed data; and PJMV: designed and performed research analyzed data and wrote the paper.

Corresponding author

Correspondence to Peter J. M. Valk.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Al Hinai, A.S.A., Grob, T., Kavelaars, F.G. et al. Archived bone marrow smears are an excellent source for NGS-based mutation detection in acute myeloid leukemia. Leukemia 34, 2220–2224 (2020). https://doi.org/10.1038/s41375-020-0744-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-020-0744-x

Search

Advanced search

Quick links