MSI2 is required for maintaining activated myelodysplastic syndrome stem cells

James Taggart; Tzu-Chieh Ho; Elianna Amin; Haiming Xu; Trevor S Barlowe; Alexendar R Perez; Benjamin H Durham; Patrick Tivnan; Rachel Okabe; Arthur Chow; Ly Vu; Sun Mi Park; Camila Prieto; Christopher Famulare; Minal Patel; Christopher J Lengner; Amit Verma; Gail Roboz; Monica Guzman; Virginia M Klimek; Omar Abdel-Wahab; Christina Leslie; Stephen D Nimer; Michael G Kharas

doi:10.1038/ncomms10739

Back

MSI2 is required for maintaining activated myelodysplastic syndrome stem cells

Journal article

Open access

Peer reviewed

MSI2 is required for maintaining activated myelodysplastic syndrome stem cells

James Taggart, Tzu-Chieh Ho, Elianna Amin, Haiming Xu, Trevor S Barlowe, Alexendar R Perez, Benjamin H Durham, Patrick Tivnan, Rachel Okabe, Arthur Chow, …

Nature communications, Vol.7(1), pp.10739-10739

2016-02-22

DOI: https://doi.org/10.1038/ncomms10739

PMCID: PMC4764878

PMID: 26898884

Abstract

Myelodysplastic Syndromes - metabolism

Humans

Leukemia, Myeloid, Acute - metabolism

Mice, Inbred C57BL

Male

Mice, Transgenic

Leukemia, Myeloid, Acute - etiology

Case-Control Studies

Myelodysplastic Syndromes - etiology

Animals

Myelodysplastic Syndromes - mortality

Hematopoietic Stem Cells - physiology

Female

Aged

RNA-Binding Proteins - metabolism

Disease Models, Animal

Myelodysplastic syndromes (MDS) are driven by complex genetic and epigenetic alterations. The MSI2 RNA-binding protein has been demonstrated to have a role in acute myeloid leukaemia and stem cell function, but its role in MDS is unknown. Here, we demonstrate that elevated MSI2 expression correlates with poor survival in MDS. Conditional deletion of Msi2 in a mouse model of MDS results in a rapid loss of MDS haematopoietic stem and progenitor cells (HSPCs) and reverses the clinical features of MDS. Inversely, inducible overexpression of MSI2 drives myeloid disease progression. The MDS HSPCs remain dependent on MSI2 expression after disease initiation. Furthermore, MSI2 expression expands and maintains a more activated (G1) MDS HSPC. Gene expression profiling of HSPCs from the MSI2 MDS mice identifies a signature that correlates with poor survival in MDS patients. Overall, we identify a role for MSI2 in MDS representing a therapeutic target in this disease.

Files and links (1)

url

https://doi.org/10.1038/ncomms10739View

Published (Version of record) Open

Metrics

13 Record Views

24 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.103 Blood Disorders; 1.103.155 Acute Myeloid Leukemia
Web Of Science research areas: Hematology
ESI research areas: Clinical Medicine

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: MSI2 is required for maintaining activated myelodysplastic syndrome stem cells
Creators: James Taggart - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Tzu-Chieh Ho - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Elianna Amin - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Haiming Xu - Memorial Sloan Kettering Cancer Center, Cancer Biology Program, New York, New York 10065, USA
Trevor S Barlowe - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Alexendar R Perez - Computational Biology Program Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Institute, New York, New York 10065, USA
Benjamin H Durham - Memorial Sloan Kettering Cancer Center, Human Oncology and Pathogenesis Program, New York, New York 10065, USA
Patrick Tivnan - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Rachel Okabe - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Arthur Chow - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Ly Vu - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Sun Mi Park - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Camila Prieto - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Christopher Famulare - Memorial Sloan Kettering Cancer Center, Department of Medicine, Leukemia Service, New York, New York 10065, USA
Minal Patel - Memorial Sloan Kettering Cancer Center, Department of Medicine, Leukemia Service, New York, New York 10065, USA
Christopher J Lengner - Department of Animal Biology, Department of Cell and Developmental Biology and Institute for Regenerative Medicine, Schools of Veterinary Medicine and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Amit Verma - Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Gail Roboz - Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA
Monica Guzman - Division of Hematology and Medical Oncology, Department of Medicine and Pharmacology, Weill Cornell Medical College, Cornell University, New York, New York 10065, USA
Virginia M Klimek - Memorial Sloan Kettering Cancer Center, Department of Medicine, Leukemia Service, New York, New York 10065, USA
Omar Abdel-Wahab - Memorial Sloan Kettering Cancer Center, Human Oncology and Pathogenesis Program, New York, New York 10065, USA
Christina Leslie - Computational Biology Program Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Institute, New York, New York 10065, USA
Stephen D Nimer - Sylvester Comprehensive Cancer Center, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA
Michael G Kharas - Molecular Pharmacology and Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Publication Details: Nature communications, Vol.7(1), pp.10739-10739
Publisher: England
Grant note: R01DK101989-01A1 / NIDDK NIH HHS 1R01CA193842-01 / NCI NIH HHS R01 DK101989 / NIDDK NIH HHS R01 CA193842 / NCI NIH HHS P30 CA008748 / NCI NIH HHS T32 GM007739 / NIGMS NIH HHS
Academic Unit: Leadership Department; Miller School of Medicine; Sylvester Comprehensive Cancer Center
Language: English
Resource Type: Journal article
PMID: 26898884
PMCID: PMC4764878
Record Identifier: 991031577842602976