Nature Communications (May 2018)
De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia
- Axel Hyrenius-Wittsten,
- Mattias Pilheden,
- Helena Sturesson,
- Jenny Hansson,
- Michael P. Walsh,
- Guangchun Song,
- Julhash U. Kazi,
- Jian Liu,
- Ramprasad Ramakrishan,
- Cristian Garcia-Ruiz,
- Stephanie Nance,
- Pankaj Gupta,
- Jinghui Zhang,
- Lars Rönnstrand,
- Anne Hultquist,
- James R. Downing,
- Karin Lindkvist-Petersson,
- Kajsa Paulsson,
- Marcus Järås,
- Tanja A. Gruber,
- Jing Ma,
- Anna K. Hagström-Andersson
Affiliations
- Axel Hyrenius-Wittsten
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Mattias Pilheden
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Helena Sturesson
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Jenny Hansson
- Division of Molecular Hematology, Department of Laboratory Medicine, Lund University
- Michael P. Walsh
- Department of Pathology, St. Jude Children´s Research Hospital
- Guangchun Song
- Department of Pathology, St. Jude Children´s Research Hospital
- Julhash U. Kazi
- Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University
- Jian Liu
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Ramprasad Ramakrishan
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Cristian Garcia-Ruiz
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Stephanie Nance
- Department of Oncology, St. Jude Children´s Research Hospital
- Pankaj Gupta
- Department of Computational Biology, St. Jude Children´s Research Hospital
- Jinghui Zhang
- Department of Computational Biology, St. Jude Children´s Research Hospital
- Lars Rönnstrand
- Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University
- Anne Hultquist
- Department of Pathology, Skane University Hospital, Lund University
- James R. Downing
- Department of Pathology, St. Jude Children´s Research Hospital
- Karin Lindkvist-Petersson
- Medical Structural Biology, Department of Experimental Medical Science, 221 84 Lund University
- Kajsa Paulsson
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Marcus Järås
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- Tanja A. Gruber
- Department of Pathology, St. Jude Children´s Research Hospital
- Jing Ma
- Department of Pathology, St. Jude Children´s Research Hospital
- Anna K. Hagström-Andersson
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University
- DOI
- https://doi.org/10.1038/s41467-018-04180-1
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 13
Abstract
In acute leukemia with KMT2A rearrangements (KMT2A-R), activating signaling mutations are common. Here, the authors use a retroviral acute myeloid mouse leukemia model to show that subclonal de novo activating mutations drive clonal evolution in acute leukemia with KMT2A-R and enhance clonal fitness.
