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Childhood hematopoietic stem cells constitute the permissive window for RUNX1-ETO leukemogenesis

  • Progress in Hematology
  • Stem cell regulation and dynamics in myeloid malignancies
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Abstract

Cancer is a very rare event at the cellular level, although it is a common disease at the body level as one third of humans die of cancer. A small subset of cells in the body harbor the cellular features that constitute a permissive window for a particular genetic change to induce cancer. The significance of a permissive window is ironically best shown by a large number of failures in generating the animal model for acute myeloid leukemia (AML) with t(8;21). Over the decades, the RUNX1-ETO fusion gene created by t(8;21) has been introduced into various types of hematopoietic cells, largely at adult stage, in mice; however, all the previous attempts failed to generate tractable AML models. In stark contrast, we recently succeeded in inducing AML with the clinical features seen in human patients by specifically introducing RUNX1-ETO in childhood hematopoietic stem cells (HSCs). This result in mice is consistent with adolescent and young adult (AYA) onset in human t(8;21) patients, and suggests that childhood HSCs constitute the permissive window for RUNX1-ETO leukemogenesis. If loss of a permissive window is induced pharmacologically, cancer cells might be selectively targeted. Such a permissive window modifier may serve as a novel therapeutic drug.

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The data supporting the findings of this review are available within the article and its references, or from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by National Medical Research Council (MOH-CIRG21nov-0007), Joint NCIS and NUS Centre for Cancer Research (N2CR) Seed Funding Programme, the National Research Foundation Singapore, the Singapore Ministry of Education under its Research Centres of Excellence initiative, and JSPS Kakenhi Grants (JP15H04312, JP16K14613, 18KT0026, 19K07668, and 22H02904).

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Mohamed Gaber Abdallah

  2. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Vania Swee Imm Teoh, Bibek Dutta & Motomi Osato

  3. Department of Microscopic and Developmental Anatomy, Tokyo Women’s Medical University, Tokyo, Japan

    Tomomasa Yokomizo

  4. International Research Center for Medical Sciences, Kumamoto University, 2-2-1 Honjo, Chuo-Ku, Kumamoto, 860-0811, Japan

    Motomi Osato

  5. Department of General Internal Medicine, Kumamoto Kenhoku Hospital, Tamana, Japan

    Motomi Osato

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  1. Mohamed Gaber Abdallah
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Correspondence to Motomi Osato.

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Abdallah, M.G., Teoh, V.S.I., Dutta, B. et al. Childhood hematopoietic stem cells constitute the permissive window for RUNX1-ETO leukemogenesis. Int J Hematol 117, 830–838 (2023). https://doi.org/10.1007/s12185-023-03605-y

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