Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis

Author:

Rampal Raajit123,Al-Shahrour Fatima4,Abdel-Wahab Omar123,Patel Jay P.1,Brunel Jean-Philippe5,Mermel Craig H.56,Bass Adam J.57,Pretz Jennifer57,Ahn Jihae1,Hricik Todd1,Kilpivaara Outi8,Wadleigh Martha7,Busque Lambert91011,Gilliland D. Gary12,Golub Todd R.51314,Ebert Benjamin L.515,Levine Ross L.123

Affiliation:

1. Human Oncology and Pathogenesis Program, and

2. Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY;

3. Weill Cornell Medical College, New York, NY;

4. Translational Bioinformatics Unit, Clinical Research Programme, Spanish National Cancer Research Centre, Madrid, Spain;

5. Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge, MA;

6. Massachusetts General Hospital, Cancer Center and Department of Pathology, Boston, MA;

7. Dana-Farber Cancer Institute, Boston, MA;

8. Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland;

9. Research Centre, Maisonneuve-Rosemont Hospital,

10. Department of Hematology, Maisonneuve-Rosemont Hospital, and

11. University of Montreal, Montreal, QC, Canada;

12. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;

13. Children's Hospital, Harvard Medical School, Boston, MA;

14. Howard Hughes Medical Institute, Chevy Chase, MD; and

15. Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Abstract

Key Points A gene expression profile consistent with activated JAK2 signaling is seen in all MPN patients, including in patients with CALR mutations. Transcriptional profiling discriminates subsets of MPNs based on JAK2V617F allele burden and on the presence of CALR and TET2 mutations.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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