Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia.

Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia. Cell Stem Cell. 2019 Aug 01;25(2):258-272.e9 Authors: McKenzie MD, Ghisi M, Oxley EP, Ngo S, Cimmino L, Esnault C, Liu R, Salmon JM, Bell CC, Ahmed N, Erlichster M, Witkowski MT, Liu GJ, Chopin M, Dakic A, Simankowicz E, Pomilio G, Vu T, Krsmanovic P, Su S, Tian L, Baldwin TM, Zalcenstein DA, DiRago L, Wang S, Metcalf D, Johnstone RW, Croker BA, Lancaster GI, Murphy AJ, Naik SH, Nutt SL, Pospisil V, Schroeder T, Wall M, Dawson MA, Wei AH, de Thé H, Ritchie ME, Zuber J, Dickins RA 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 m...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research