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Xist RNA is a potent suppressor of hematologic cancer in mice.

Publication ,  Journal Article
Yildirim, E; Kirby, JE; Brown, DE; Mercier, FE; Sadreyev, RI; Scadden, DT; Lee, JT
Published in: Cell
February 14, 2013

X chromosome aneuploidies have long been associated with human cancers, but causality has not been established. In mammals, X chromosome inactivation (XCI) is triggered by Xist RNA to equalize gene expression between the sexes. Here we delete Xist in the blood compartment of mice and demonstrate that mutant females develop a highly aggressive myeloproliferative neoplasm and myelodysplastic syndrome (mixed MPN/MDS) with 100% penetrance. Significant disease components include primary myelofibrosis, leukemia, histiocytic sarcoma, and vasculitis. Xist-deficient hematopoietic stem cells (HSCs) show aberrant maturation and age-dependent loss. Reconstitution experiments indicate that MPN/MDS and myelofibrosis are of hematopoietic rather than stromal origin. We propose that Xist loss results in X reactivation and consequent genome-wide changes that lead to cancer, thereby causally linking the X chromosome to cancer in mice. Thus, Xist RNA not only is required to maintain XCI but also suppresses cancer in vivo.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 14, 2013

Volume

152

Issue

4

Start / End Page

727 / 742

Location

United States

Related Subject Headings

  • X Chromosome Inactivation
  • Splenomegaly
  • RNA, Long Noncoding
  • Primary Myelofibrosis
  • Myeloproliferative Disorders
  • Myelodysplastic Syndromes
  • Mice
  • Male
  • Hematopoietic Stem Cells
  • Genes, Tumor Suppressor
 

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Yildirim, E., Kirby, J. E., Brown, D. E., Mercier, F. E., Sadreyev, R. I., Scadden, D. T., & Lee, J. T. (2013). Xist RNA is a potent suppressor of hematologic cancer in mice. Cell, 152(4), 727–742. https://doi.org/10.1016/j.cell.2013.01.034
Yildirim, Eda, James E. Kirby, Diane E. Brown, Francois E. Mercier, Ruslan I. Sadreyev, David T. Scadden, and Jeannie T. Lee. “Xist RNA is a potent suppressor of hematologic cancer in mice.Cell 152, no. 4 (February 14, 2013): 727–42. https://doi.org/10.1016/j.cell.2013.01.034.
Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, et al. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell. 2013 Feb 14;152(4):727–42.
Yildirim, Eda, et al. “Xist RNA is a potent suppressor of hematologic cancer in mice.Cell, vol. 152, no. 4, Feb. 2013, pp. 727–42. Pubmed, doi:10.1016/j.cell.2013.01.034.
Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI, Scadden DT, Lee JT. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell. 2013 Feb 14;152(4):727–742.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 14, 2013

Volume

152

Issue

4

Start / End Page

727 / 742

Location

United States

Related Subject Headings

  • X Chromosome Inactivation
  • Splenomegaly
  • RNA, Long Noncoding
  • Primary Myelofibrosis
  • Myeloproliferative Disorders
  • Myelodysplastic Syndromes
  • Mice
  • Male
  • Hematopoietic Stem Cells
  • Genes, Tumor Suppressor