'Did He Who Made the Lamb Make Thee?' New Developments in Treating the 'Fearful Symmetry' of Acute Myeloid Leukemia

Gabriela Brumatti; Najoua Lalaoui; Andrew H Wei; John Silke

doi:10.1016/j.molmed.2017.01.005

'Did He Who Made the Lamb Make Thee?' New Developments in Treating the 'Fearful Symmetry' of Acute Myeloid Leukemia

Trends Mol Med. 2017 Mar;23(3):264-281. doi: 10.1016/j.molmed.2017.01.005. Epub 2017 Feb 11.

Authors

Gabriela Brumatti¹, Najoua Lalaoui¹, Andrew H Wei², John Silke³

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
² Alfred Hospital and Monash University, Melbourne, Australia.
³ The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia. Electronic address: silke@wehi.edu.au.

PMID: 28196625
DOI: 10.1016/j.molmed.2017.01.005

Abstract

Malignant cells must circumvent endogenous cell death pathways to survive and develop into cancers. Acquired cell death resistance also sets up malignant cells to survive anticancer therapies. Acute Myeloid Leukemia (AML) is an aggressive blood cancer characterized by high relapse rate and resistance to cytotoxic therapies. Recent collaborative profiling projects have led to a greater understanding of the 'fearful symmetry' of the genomic landscape of AML, and point to the development of novel potential therapies that can overcome factors linked to chemoresistance. We review here the most recent research in the genetics of AML and how these discoveries have led, or might lead, to therapies that specifically activate cell death pathways to substantially challenge this 'fearful' disease.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Cell Death / drug effects*
DNA Modification Methylases / antagonists & inhibitors
Humans
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism
Leukemia, Myeloid, Acute / pathology
Molecular Targeted Therapy / methods
Peptidomimetics / pharmacology
Peptidomimetics / therapeutic use
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Signal Transduction / drug effects*

Substances

Antineoplastic Agents
Peptidomimetics
Protein Kinase Inhibitors
DNA Modification Methylases