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Non-coding RNAs

The cancer X factor

Nature Reviews Cancer volume 13, pages 224–225 (2013)Cite this article

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loss of Xist ... can cause haematopoietic cancers in mice

To understand post-XCI functions for Xist, the authors conditionally knocked out Xist (XistΔ) in mouse haematopoietic stem cells (HSCs) after the establishment of XCI (embryonic day 10.5). Both XistΔ/Δ and XistΔ/+ mutant females began to die at about 1.5 months of age, and only 10% survived to 2 years; this did not occur in males, and there was no difference between XistΔ/Δ and XistΔ/+ females. Necropsy of deceased animals showed massive splenomegaly, with changes suggestive of extramedullary haematopoiesis (the formation of new blood cells outside of the bone marrow) beyond physiological levels. Although hyperproliferation of all haematopoietic lineages was observed, myeloid cells had a competitive advantage. Bone marrow dysfunction, including myelofibrosis (the replacement of marrow with fibrotic tissue) was also evident, and haematopoiesis was abnormal in both the bone marrow and the extramedullary sites, leading to myeloproliferation and myelodysplasia. The mice had evidence of chronic myelomonocytic leukaemia (CMML), erythroleukaemia, histiocytic sarcoma and vasculitis, which coexisted to different degrees and which led to different clinical outcomes. Overall, these defects support a diagnosis of mixed myeloproliferative neoplasm and myelodysplastic syndrome (MPN/MDS); notably, CMML, erythroleukaemia and myelofibrosis are components of human MPN/MDS.

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ORIGINAL RESEARCH PAPER

  1. Yildirim, E. et al. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152, 727–742 (2013)

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  1. Sarah Seton-Rogers
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Seton-Rogers, S. The cancer X factor. Nat Rev Cancer 13, 224–225 (2013). https://doi.org/10.1038/nrc3489

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