Nature Communications (May 2021)
RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis
- Ryan M. Carr,
- Denis Vorobyev,
- Terra Lasho,
- David L. Marks,
- Ezequiel J. Tolosa,
- Alexis Vedder,
- Luciana L. Almada,
- Andrey Yurcheko,
- Ismael Padioleau,
- Bonnie Alver,
- Giacomo Coltro,
- Moritz Binder,
- Stephanie L. Safgren,
- Isaac Horn,
- Xiaona You,
- Eric Solary,
- Maria E. Balasis,
- Kurt Berger,
- James Hiebert,
- Thomas Witzig,
- Ajinkya Buradkar,
- Temeida Graf,
- Peter Valent,
- Abhishek A. Mangaonkar,
- Keith D. Robertson,
- Matthew T. Howard,
- Scott H. Kaufmann,
- Christopher Pin,
- Martin E. Fernandez-Zapico,
- Klaus Geissler,
- Nathalie Droin,
- Eric Padron,
- Jing Zhang,
- Sergey Nikolaev,
- Mrinal M. Patnaik
Affiliations
- Ryan M. Carr
- Division of Hematology, Department of Internal Medicine
- Denis Vorobyev
- INSERM U981, Gustave Roussy Cancer Center
- Terra Lasho
- Division of Hematology, Department of Internal Medicine
- David L. Marks
- Schulze Center for Novel Therapeutics, Division of Oncology Research
- Ezequiel J. Tolosa
- Schulze Center for Novel Therapeutics, Division of Oncology Research
- Alexis Vedder
- Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center
- Luciana L. Almada
- Schulze Center for Novel Therapeutics, Division of Oncology Research
- Andrey Yurcheko
- INSERM U981, Gustave Roussy Cancer Center
- Ismael Padioleau
- INSERM U981, Gustave Roussy Cancer Center
- Bonnie Alver
- Molecular Pharmacology and Experimental Therapeutics
- Giacomo Coltro
- Division of Hematology, Department of Internal Medicine
- Moritz Binder
- Division of Hematology, Department of Internal Medicine
- Stephanie L. Safgren
- Schulze Center for Novel Therapeutics, Division of Oncology Research
- Isaac Horn
- Schulze Center for Novel Therapeutics, Division of Oncology Research
- Xiaona You
- McArdle Laboratory for Cancer Research, University of Wisconsin-Madison
- Eric Solary
- INSERM U1170 and Department of Hematology, Gustave Roussy Cancer Center
- Maria E. Balasis
- Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center
- Kurt Berger
- London Regional Transgenic and Gene Targeting Facility, Lawson Health Research Institute University of Western Ontario
- James Hiebert
- Division of Hematology, Department of Internal Medicine
- Thomas Witzig
- Division of Hematology, Department of Internal Medicine
- Ajinkya Buradkar
- Division of Hematology, Department of Internal Medicine
- Temeida Graf
- 5TH Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna
- Peter Valent
- 5TH Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna
- Abhishek A. Mangaonkar
- Division of Hematology, Department of Internal Medicine
- Keith D. Robertson
- Molecular Pharmacology and Experimental Therapeutics
- Matthew T. Howard
- Department of Laboratory Medicine and Pathology
- Scott H. Kaufmann
- Division of Hematology, Department of Internal Medicine
- Christopher Pin
- London Regional Transgenic and Gene Targeting Facility, Lawson Health Research Institute University of Western Ontario
- Martin E. Fernandez-Zapico
- Schulze Center for Novel Therapeutics, Division of Oncology Research
- Klaus Geissler
- Sigmund Freud University Vienna
- Nathalie Droin
- INSERM U1170 and Department of Hematology, Gustave Roussy Cancer Center
- Eric Padron
- Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center
- Jing Zhang
- McArdle Laboratory for Cancer Research, University of Wisconsin-Madison
- Sergey Nikolaev
- INSERM U981, Gustave Roussy Cancer Center
- Mrinal M. Patnaik
- Division of Hematology, Department of Internal Medicine
- DOI
- https://doi.org/10.1038/s41467-021-23186-w
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 18
Abstract
Chronic myelomonocytic leukaemia is classified as proliferative (pCMML) or dysplastic based on the white blood cell counts but biological differences are unclear. Here, the authors show genetic, transcriptomic and epigenomic differences between these two subtypes establishing that pCMML is RAS-pathway driven and that inhibiting RAS-driven PLK1 expression is a viable therapeutic target.
