Disease evolution and outcomes in familial AML with germline CEBPA mutations

Author:

Tawana Kiran1,Wang Jun2,Renneville Aline345,Bödör Csaba6,Hills Robert7,Loveday Chey1,Savic Aleksandar8,Van Delft Frederik W.910,Treleaven Jennifer10,Georgiades Panayiotis1,Uglow Elizabeth1,Asou Norio11,Uike Naokuni12,Debeljak Maruša13,Jazbec Janez14,Ancliff Philip15,Gale Rosemary16,Thomas Xavier17,Mialou Valerie18,Döhner Konstanze19,Bullinger Lars19,Mueller Beatrice20,Pabst Thomas20,Stelljes Matthias21,Schlegelberger Brigitte22,Wozniak Eva23,Iqbal Sameena1,Okosun Jessica1,Araf Shamzah1,Frank Anne-Katrine24,Lauridsen Felicia B.24,Porse Bo242526,Nerlov Claus27,Owen Carolyn28,Dokal Inderjeet29,Gribben John1,Smith Matthew1,Preudhomme Claude345,Chelala Claude2,Cavenagh Jamie1,Fitzgibbon Jude1

Affiliation:

1. Centre for Haemato-Oncology, Barts Cancer Institute, London, United Kingdom;

2. Centre for Molecular Oncology, Barts Cancer Institute, London, United Kingdom;

3. Laboratory of Hematology, Biology and Pathology Center, Centre Hospitalier Régional Universitaire of Lille, Lille, France;

4. University of Lille Nord de France, Lille, France;

5. Inserm, UMR387, Team 3, Cancer Research Institute of Lille, Lille, France;

6. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary;

7. School of Medicine, Cardiff University, Cardiff, United Kingdom;

8. Clinic of Hematology, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia;

9. Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom;

10. The Institute of Cancer Research, Department of Haemato-Oncology, Sutton, United Kingdom;

11. Department of Hematology, International Medical Center, Saitama Medical University, Hidaka, Japan;

12. Department of Hematology, National Kyushu Cancer Center, Fukuoka, Japan;

13. Unit for Special laboratory Diagnostics, University Children's Hospital University Medical Center, Ljubljana, Slovenia;

14. Unit for Hematology and Oncology, University Children's Hospital University Medical Center, Ljubljana, Slovenia;

15. Department of Haematology, Great Ormond St Hospital, London, United Kingdom;

16. Department of Haematology, University College London Cancer Institute, London, United Kingdom;

17. Department of Hematology, Lyon Sud Hospital, Pierre-Bénite, France;

18. Institute of Pediatric Hematology and Oncology, Lyon Hospital, Lyon, France;

19. Department of Internal Medicine III, University of Ulm, Ulm, Germany;

20. Hematology/Oncology, Department for Clinical Research and Pediatrics, University Hospital Berne and University Berne, Berne, Switzerland;

21. Department of Medicine/Hematology and Oncology, University of Muenster, Muenster, Germany;

22. Institute of Human Genetics, Hannover Medical School, Hannover, Germany;

23. Genome Centre, Barts and the London School of Medicine and Dentristry, London, United Kingdom;

24. The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;

25. Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark;

26. Danish Stem Cell Centre (DanStem) Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark;

27. Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;

28. Division of Hematology and Hematological Malignancies, Foothills Medical Centre, Calgary, Canada; and

29. Centre for Paediatrics, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom

Abstract

Key Points Germ-line CEBPA mutations are highly penetrant, causing early-onset de novo AML associated with favorable survival outcomes. Familial CEBPA-mutated AML displays a unique model of disease progression, with recurrence caused by novel, independent leukemic episodes.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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