Childhood Hematopoietic Stem Cells Constitute the Permissive Window for RUNX1-ETO Leukemogenesis

Overview

Journal Int J Hematol

Specialty Hematology

Date 2023 May 2

PMID 37129801

Authors

Mohamed Gaber Abdallah

Vania Swee Imm Teoh

Bibek Dutta

Tomomasa Yokomizo

Motomi Osato

Affiliations

Soon will be listed here.

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.

Citing Articles

Stem cell regulation and dynamics in myeloid malignancies.

Sashida G Int J Hematol. 2023; 117(6):789-790.

PMID: 37191835 DOI: 10.1007/s12185-023-03615-w.

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