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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yildirim, E; Kirby, JE; Brown, DE; Mercier, FE; Sadreyev, RI; Scadden, DT; Lee, JT

Published Date

  • February 14, 2013

Published In

Volume / Issue

  • 152 / 4

Start / End Page

  • 727 - 742

PubMed ID

  • 23415223

Pubmed Central ID

  • 23415223

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2013.01.034

Language

  • eng

Conference Location

  • United States