Overlapping features of therapy-related and de novo <i>NPM1</i>-mutated AML-Reference-Cited by-同舟云学术

Overlapping features of therapy-related and de novo NPM1-mutated AML

Published:2023-04-13 Issue:15 Volume:141 Page:1846-1857
ISSN:0006-4971
Container-title:Blood
language:en
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Author:

Othman Jad¹²^ORCID,Meggendorfer Manja³,Tiacci Enrico⁴,Thiede Christian⁵^ORCID,Schlenk Richard⁶^ORCID,Dillon Richard¹²^ORCID,Stasik Sebastian⁵^ORCID,Venanzi Alessandra⁴,Bertoli Sarah⁷^ORCID,Delabesse Eric⁷,Dumas Pierre-Yves⁸^ORCID,Pigneux Arnaud⁸,Bidet Audrey⁸,Gilkes Amanda F.⁹,Thomas Ian⁹,Voso Maria Teresa¹⁰^ORCID,Rambaldi Alessandro¹¹^ORCID,Brunetti Lorenzo¹²^ORCID,Perriello Vincenzo M.⁴,Andresen Vibeke¹³^ORCID,Gjertsen Bjorn T.¹³,Martelli Maria Paola⁴^ORCID,Récher Christian⁷,Röllig Christoph⁵^ORCID,Bornhäuser Martin⁵,Serve Hubert¹⁴^ORCID,Müller-Tidow Carsten⁶^ORCID,Baldus Claudia D.¹⁵,Haferlach Tortsten³,Russell Nigel²¹⁶,Falini Brunangelo⁴^ORCID

Affiliation:

1. 1Department of Medical and Molecular Genetics, King’s College, London, United Kingdom

2. 2Department of Haematology, Guy’s and St Thomas Hospitals NHS Trust, London, United Kingdom

3. 3MLL Munich Leukemia Laboratory, Munich, Germany

4. 4Institute of Hematology and Center for Hemato-Oncology Research (CREO), Department of Medicine and Surgery, University and Hospital of Perugia, Perugia, Italy

5. 5University Hospital, Medical Clinic I, Dresden University of Technology, Dresden, Germany

6. 6Department of Hematology/Oncology and NCT Trial Center, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg, Germany

7. 7Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France

8. 8Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

9. 9Department of Hematology and Centre for Trials Research, School of Medicine, Cardiff University, Cardiff, United Kingdom

10. 10Institute of Hematology, University of Tor Vergata, Rome, Italy

11. 11Department of Oncology and Hematology, University of Milan and Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

12. 12Università Politecnica delle Marche, Ancona, Italy

13. 13Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, Bergen, Norway

14. 14Department of Medicine, Hematology/Oncology, Goethe University Frankfurt, Frankfurt, Germany

15. 15Universitätsklinikum Schleswig-Holstein, Kiel, Germany

16. 16Nottingham University, Nottingham, United Kingdom

Abstract

Abstract NPM 1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of “therapy-related” NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared the genetics, transcriptional profile, and clinical outcomes of t-NPM1 AML, de novo NPM1-mutated AML (dn-NPM1 AML), and therapy-related AML (t-AML) with wild-type NPM1 (t-AML). Normal karyotype was more frequent in t-NPM1 AML (n = 78/96, 88%) and dn-NPM1 (n = 1986/2394, 88%) than in t-AML (n = 103/390, 28%; P < .001). DNMT3A and TET2 were mutated in 43% and 40% of t-NPM1 AML (n = 107), similar to dn-NPM1 (n = 88, 48% and 30%; P > 0.1), but more frequently than t-AML (n = 162; 14% and 10%; P < 0.001). Often mutated in t-AML, TP53 and PPM1D were wild-type in 97% and 96% of t-NPM1 AML, respectively. t-NPM1 and dn-NPM1 AML were transcriptionally similar, (including HOX genes upregulation). At 62 months of median follow-up, the 3-year overall survival (OS) for t-NPM1 AML (n = 96), dn-NPM1 AML (n = 2394), and t-AML (n = 390) were 54%, 60%, and 31%, respectively. In multivariable analysis, OS was similar for the NPM1-mutated groups (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.65-1.25; P = .45), but better in t-NPM1 AML than in t-AML (HR, 1.86; 95% CI, 1.30-2.68; P < .001). Relapse-free survival was similar between t-NPM1 and dn-NPM1 AML (HR, 1.02; 95% CI, 0.72-1.467; P = .90), but significantly higher in t-NPM1 AML versus t-AML (HR, 1.77; 95% CI, 1.19-2.64; P = .0045). t-NPM1 and dn-NPM1 AML have overlapping features, suggesting that they should be classified as a single disease entity.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Link

https://ashpublications.org/blood/article-pdf/141/15/1846/2044678/blood_bld-2022-018108-main.pdf

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