Shira N Dinner1, Francis J Giles, Jessica K Altman. 1. Division of Hematology/Oncology and Northwestern Medicine Developmental Therapeutics Institute, Robert H. Lurie Comprehensive Cancer Center, Northwestern University-Feinberg School of Medicine, Chicago, Illinois, USA.
Abstract
PURPOSE OF REVIEW: Although frontline treatment of acute myeloid leukemia (AML) achieves high remission rates, approximately 75-80% of patients will either not respond to or relapse after initial therapy. Some patients, generally those who are younger, can be successfully salvaged with second-line chemotherapy followed by allogeneic stem cell transplantation. There is a great need for novel therapies in AML. RECENT FINDINGS: Advances in molecular technology recently identified recurrent mutations including mutations of DNMT3A, IDH1/2, and TET2. These mutations represent a major advance in the understanding of leukemogenesis and prognosis, and have enabled the development of targeted therapies. SUMMARY: Improved knowledge of the molecular pathogenesis of AML has allowed development of therapies targeting epigenetic modulation, intracellular signaling pathways, prosurvival proteins, and the tumor microenvironment.
PURPOSE OF REVIEW: Although frontline treatment of acute myeloid leukemia (AML) achieves high remission rates, approximately 75-80% of patients will either not respond to or relapse after initial therapy. Some patients, generally those who are younger, can be successfully salvaged with second-line chemotherapy followed by allogeneic stem cell transplantation. There is a great need for novel therapies in AML. RECENT FINDINGS: Advances in molecular technology recently identified recurrent mutations including mutations of DNMT3A, IDH1/2, and TET2. These mutations represent a major advance in the understanding of leukemogenesis and prognosis, and have enabled the development of targeted therapies. SUMMARY: Improved knowledge of the molecular pathogenesis of AML has allowed development of therapies targeting epigenetic modulation, intracellular signaling pathways, prosurvival proteins, and the tumor microenvironment.
Authors: Mark A Gregory; Angelo D'Alessandro; Francesca Alvarez-Calderon; Jihye Kim; Travis Nemkov; Biniam Adane; Andrii I Rozhok; Amit Kumar; Vijay Kumar; Daniel A Pollyea; Michael F Wempe; Craig T Jordan; Natalie J Serkova; Aik Choon Tan; Kirk C Hansen; James DeGregori Journal: Proc Natl Acad Sci U S A Date: 2016-10-10 Impact factor: 11.205