Journal article
Interconversion between Tumorigenic and Differentiated States in Acute Myeloid Leukemia
MD McKenzie, M Ghisi, EP Oxley, S Ngo, L Cimmino, C Esnault, R Liu, JM Salmon, CC Bell, N Ahmed, M Erlichster, MT Witkowski, GJ Liu, M Chopin, A Dakic, E Simankowicz, G Pomilio, T Vu, P Krsmanovic, S Su Show all
Cell Stem Cell | Published : 2019
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..
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Awarded by Boehringer Ingelheim
Funding Acknowledgements
We thank B. Coghlan, S. Brown, K. Stoev, C. Alvarado, L. Whitehead, M. Scott, M. Lee, S. Dietrich, and M. Halemba for technical assistance; G. Paukovics, E. Orlowski-Oliver, and M. Costa at the AMREP Flow Facility; S. Wilcox, M. Everest, Y. Zhang, B. Whittle, S. Macraild, and F. Brown for NGS; S. Fleming, M. Gorniak, and A. Ivey at the Alfred Hospital; S. Lowe and L. Dow for MSCV-IRES-tTA; and B. Kile, D. Curtis, S. Ting, J. Hamilton, A. Perkins, M. Plebanski, and members of the Dickins laboratory for insights. This study was supported by the National Health and Medical Research Council of Australia (NHMRC) project grant 1057854, Australian Government NHMRC IRIISS, Victorian State Government OIS grants, an Australian Research Council Future Fellowship (S.L.N.), Gabrielle's Angel Foundation for Cancer Research (B.A.C.), SNF grant 179490 (T.S.), AZV 16-31586A UNCE/MED/016 Progres Q26 (V.P.), Boehringer Ingelheim (J.Z.), Leukaemia Foundation of Australia Postdoctoral Fellowship (M.D.M.), NHRMC Career Development Fellowship 1104924 (M.E.R.), a Sylvia and Charles Viertel Charitable Foundation Fellowship (R.A.D.), and a Victorian Endowment for Science, Knowledge and Innovation (VESKI) Fellowship (R.A.D. and M.A.D.).