Interconversion between tumorigenic and differentiated states in acute myeloid leukemia
Details
Publication Year 2019-08-01, Volume 25, Issue #2, Page 258-272 e9
Journal Title
Cell Stem Cell
Publication Type
Journal Article
Abstract
Tumors are composed of phenotypically heterogeneous cancer cells that often resemble various differentiation states of their lineage of origin. Within this hierarchy, it is thought that an immature subpopulation of tumor-propagating cancer stem cells (CSCs) differentiates into non-tumorigenic progeny, providing a rationale for therapeutic strategies that specifically eradicate CSCs or induce their differentiation. The clinical success of these approaches depends on CSC differentiation being unidirectional rather than reversible, yet this question remains unresolved even in prototypically hierarchical malignancies, such as acute myeloid leukemia (AML). Here, we show in murine and human models of AML that, upon perturbation of endogenous expression of the lineage-determining transcription factor PU.1 or withdrawal of established differentiation therapies, some mature leukemia cells can de-differentiate and reacquire clonogenic and leukemogenic properties. Our results reveal plasticity of CSC maturation in AML, highlighting the need to therapeutically eradicate cancer cells across a range of differentiation states.
Publisher
Cell Press
WEHI Research Division(s)
Immunology; Epigenetics And Development; Blood Cells And Blood Cancer
PubMed ID
31374198
NHMRC Grants
NHMRC/1104924
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-08-13 12:35:11
Last Modified: 2019-08-13 01:03:08
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