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Acute myeloid leukemia

New strategies to treat AML: novel insights into AML survival pathways and combination therapies

Abstract

The effective treatment of acute myeloid leukemia (AML) is very challenging. Due to the immense heterogeneity of this disease, treating it using a “one size fits all” approach is ineffective and only benefits a subset of patients. Instead, there is a shift towards more personalized treatment based on the patients’ genomic signature. This shift has facilitated the increased revelation of novel insights into pathways that lead to the survival and propagation of AML cells. These AML survival pathways are involved in drug resistance, evasion of the immune system, reprogramming metabolism, and impairing differentiation. In addition, based on the reports of enhanced clinical efficiencies when combining drugs or treatments, deeper investigation into possible pathways, which can be targeted together to increase treatment response in a wider group of patients, is warranted. In this review, not only is a comprehensive summary of targets involved in these pathways provided, but also insights into the potential of targeting these molecules in combination therapy will be discussed.

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Fig. 1: Graphical summary of novel insights into pathways that contribute to AML survival.

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Acknowledgements

We apologize to colleagues whose work could not be cited due to space constraints. We thank Dr. Oliver T. Keppler for continuous support and Dr. Constanze Schneider for critical reading of the manuscript. HMB acknowledges funding from the Wilhelm-Sander Stiftung (2017.122.1). RN is supported by the graduate program Infection Research on Human Pathogens@MvPI at Max von Pettenkofer Institute, LMU. AS-I is supported by the Max Weber-Program of the State of Bavaria. Open Access funding enabled and organized by Projekt DEAL.

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41375_2020_1069_MOESM1_ESM.pdf

Ceramide and sphingosine-1-phosphate (S1P) are involved in pro-apoptotic and pro-survival signaling of AML cells, respectively, as well as drug sensitivity.

PFKFB3 is an important switch between glycolysis and the pentose phosphate pathway (PPP).

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Nair, R., Salinas-Illarena, A. & Baldauf, HM. New strategies to treat AML: novel insights into AML survival pathways and combination therapies. Leukemia 35, 299–311 (2021). https://doi.org/10.1038/s41375-020-01069-1

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