Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia

Author:

Dovey Oliver M.1,Cooper Jonathan L.1,Mupo Annalisa1,Grove Carolyn S.123,Lynn Claire4,Conte Nathalie5,Andrews Robert M.6,Pacharne Suruchi1,Tzelepis Konstantinos1,Vijayabaskar M. S.1,Green Paul1,Rad Roland78,Arends Mark9,Wright Penny10,Yusa Kosuke1,Bradley Allan1,Varela Ignacio11,Vassiliou George S.110ORCID

Affiliation:

1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom;

2. School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Australia;

3. PathWest Division of Clinical Pathology, Queen Elizabeth II Medical Centre, Nedlands, Australia;

4. Leukemia and Stem Cell Biology Group, Division of Cancer Studies, Department of Haematological Medicine, King's College London, London, United Kingdom;

5. Sample Phenotype Ontology Team, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom;

6. Institute of Translation, Innovation, Methodology, and Engagement, Cardiff University School of Medicine, Cardiff, United Kingdom;

7. Department of Medicine II, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany;

8. German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany;

9. Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;

10. Department of Haematology, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom; and

11. Instituto de Biomedicina y Biotecnología de Cantabria, Santander, Spain

Abstract

Key Points Npm1c and Nras-G12D co-mutation in mice leads to AML with a longer latency and a more mature phenotype than the Npm1c/Flt3-ITD combination. Mutant Flt3 or Nras allele amplification is the dominant mode of progression in both Npm1c/Flt3-ITD and Npm1c/Nras-G12D murine AML.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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