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

Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy

Leukemia volume 37, pages 240–243 (2023)Cite this article

Subjects

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

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Fig. 1: Overall survival by TP53 mutation status.

Data availability

Original data are available from the corresponding author at request.

References

  1. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel. Blood. 2022;140:1345–77.

  2. Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020;26:1549–56.

  3. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–21.

    Article  CAS  Google Scholar 

  4. Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Ossa JEA, Nannya Y, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1:EVIDoa2200008.

    Article  Google Scholar 

  5. Weinberg OK, Siddon AJ, Madanat Y, Gagan J, Arber DA, Dal Cin P, et al. TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Blood Adv. 2022;6:2847–53.

  6. Grob T, Al Hinai ASA, Sanders MA, Kavelaars FG, Rijken M, Gradowska PL, et al. Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2022;139:2347–54.

    Article  CAS  Google Scholar 

  7. Tashakori M, Kadia TM, Loghavi S, Daver NG, Kanagal-Shamanna R, Pierce SR, et al. TP53 copy number and protein expression inform mutation status across risk categories in acute myeloid leukemia. Blood. 2022;140:58–72.

  8. Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. International consensus classification of myeloid neoplasms and acute leukemia: integrating morphological, clinical, and genomic data. Blood. 2022;140:1200–28.

  9. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the world health organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36:1703–19.

    Article  Google Scholar 

  10. Shallis RM, Bewersdorf JP, Stahl MF, Halene S, Zeidan AM. Are we moving the needle for patients with TP53-mutated acute myeloid leukemia? Cancers (Basel). 2022;14:2434.

  11. Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020;26:1549–56.

    Article  CAS  Google Scholar 

  12. Zeidan AM, Boss I, Beach CL, Copeland WB, Thompson E, Fox BA, et al. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes. Blood Adv. 2022;6:2207–18.

    Article  CAS  Google Scholar 

  13. Zeidan AM, Boss I, Beach CL, Copeland WB, Thompson E, Fox BA, et al. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML. Blood Adv. 2022;6:2219–29.

    Article  CAS  Google Scholar 

  14. Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21:4642–9.

    Article  Google Scholar 

  15. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–25.

    Article  CAS  Google Scholar 

  16. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383:617–29.

    Article  CAS  Google Scholar 

  17. Greenberg PL, Stone RM, Al-Kali A, Bennett JM, Borate U, Brunner AM, et al. NCCN Guidelines® insights: myelodysplastic syndromes, version 3.2022. J Natl Compr Canc Netw. 2022;20:106–17.

    Article  Google Scholar 

Download references

Acknowledgements

AMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research.

Author information

Author notes

  1. These authors contributed equally: Amer M. Zeidan, Jan Philipp Bewersdorf.

Authors and Affiliations

  1. Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, Yale University, New Haven, CT, USA

    Amer M. Zeidan, Jan Philipp Bewersdorf, Rory M. Shallis & Stephanie Halene

  2. Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jan Philipp Bewersdorf

  3. Bristol Myers Squibb, Princeton, NJ, USA

    Vanessa Hasle, Ethan Thompson, Daniel Lopes de Menezes, Shelonidta Rose, Isaac Boss & Brian Fox

  4. MLL Munich Leukemia Laboratory, Munich, Germany

    Torsten Haferlach

Authors
  1. Amer M. Zeidan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan Philipp Bewersdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vanessa Hasle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rory M. Shallis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ethan Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel Lopes de Menezes
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shelonidta Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Isaac Boss
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephanie Halene
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Torsten Haferlach
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Brian Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JPB, BF, and AMZ conceptualized the study. BF, VH, ET, and TH performed data analyses. JPB and AMZ wrote the initial manuscript draft. All authors interpreted data and contributed to subsequent drafts of the manuscript.

Corresponding author

Correspondence to Amer M. Zeidan.

Ethics declarations

Competing interests

AMZ received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Cardiff oncology, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, and Tyme. AMZ served on clinical trial committees for Novartis, Abbvie, Gilead, BioCryst, Abbvie, ALX Oncology, Geron and Celgene/BMS. RMS participated in advisory boards, and/or had a consultancy with and received honoraria from Bristol Myers Squibb and Gilead Sciences, Inc; divested equity interest in Curis Oncology. IB, ET, BAF, VEH, and SR are employees of Celgene, a Bristol Myers Squibb company, and may be shareholders. SH has received research funding received honoraria from FORMA Therapeutics. TH is the owner of Munich Leukemia Laboratory. All other authors have no relevant conflicts of interest to declare.

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

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zeidan, A.M., Bewersdorf, J.P., Hasle, V. et al. Prognostic implications of mono-hit and multi-hit TP53 alterations in patients with acute myeloid leukemia and higher risk myelodysplastic syndromes treated with azacitidine-based therapy. Leukemia 37, 240–243 (2023). https://doi.org/10.1038/s41375-022-01766-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-022-01766-z

Search

Advanced search

Quick links