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PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention

Author

Listed:
  • Jiwang Zhang

    (Stowers Institute for Medical Research)

  • Justin C. Grindley

    (Stowers Institute for Medical Research)

  • Tong Yin

    (Stowers Institute for Medical Research)

  • Sachintha Jayasinghe

    (Stowers Institute for Medical Research)

  • Xi C. He

    (Stowers Institute for Medical Research)

  • Jason T. Ross

    (Stowers Institute for Medical Research)

  • Jeffrey S. Haug

    (Stowers Institute for Medical Research)

  • Dawn Rupp

    (Stowers Institute for Medical Research)

  • Kimberly S. Porter-Westpfahl

    (Stowers Institute for Medical Research)

  • Leanne M. Wiedemann

    (Stowers Institute for Medical Research
    Kansas University Medical Center)

  • Hong Wu

    (UCLA School of Medicine)

  • Linheng Li

    (Stowers Institute for Medical Research
    Kansas University Medical Center)

Abstract

Cancer stem cell function Stem cells that initiate and maintain cancers are so like normal stem cells that it's hard to design drugs to target them specifically. This is a serious problem as, for example, damaging blood stem cells in leukaemia therapy can cause haematopoietic failure and death. Now a study of the tumour suppressor PTEN, often inactivated in leukaemia and other cancers, pinpoints a major difference between self-renewal in normal and cancer stem cells. PTEN normally inhibits the phosphatidylinositol-3-OH kinase signalling pathway, limiting cell proliferation and survival. In the absence of PTEN, leukaemic stem cells proliferate, but normal stem cells are depleted. This suggests that PTEN-mimicking drugs may act against leukaemia yet preserve blood stem cells. Indeed, in Pten-deficient mice rapamycin kills leukaemic stem cells but rescues normal stem cell function. A separate study confirms PTEN's role in blood stem cell regulation.

Suggested Citation

  • Jiwang Zhang & Justin C. Grindley & Tong Yin & Sachintha Jayasinghe & Xi C. He & Jason T. Ross & Jeffrey S. Haug & Dawn Rupp & Kimberly S. Porter-Westpfahl & Leanne M. Wiedemann & Hong Wu & Linheng Li, 2006. "PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention," Nature, Nature, vol. 441(7092), pages 518-522, May.
    • Handle: RePEc:nat:nature:v:441:y:2006:i:7092:d:10.1038_nature04747
    DOI: 10.1038/nature04747
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    Cited by:

    1. Hongna Zuo & Aiwei Wu & Mingwei Wang & Liquan Hong & Hu Wang, 2024. "tRNA m1A modification regulate HSC maintenance and self-renewal via mTORC1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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