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      Acute myeloid leukemia: current progress and future directions

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          Abstract

          Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.

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          Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

          Hartmut Döhner, Elihu Estey, David Grimwade … (2017)
          The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
          Article 0 comments Cited 1423 times – based on 0 reviews     Review now
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            Genomic Classification and Prognosis in Acute Myeloid Leukemia

            Elli Papaemmanuil, Moritz Gerstung, Lars Bullinger … (2016)
            New England Journal of Medicine, 374(23), 2209-2221
            Article 0 comments Cited 889 times – based on 0 reviews     Review now
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              Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia.

              Timothy Ley, Christopher Miller, Li Ding … (2013)
              Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined. The relationships between patterns of mutations and epigenetic phenotypes are not yet clear. We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis. AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes. Of these, an average of 5 are in genes that are recurrently mutated in AML. A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples. Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcription-factor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumor-suppressor genes (16%), DNA-methylation-related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%). Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories. We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients. The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification. (Funded by the National Institutes of Health.).
              Article 0 comments Cited 814 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Hagop Kantarjian:
                ORCID: http://orcid.org/0000-0002-1908-3307
                hkantarjian@mdanderson.org
                Journal
                Journal ID (nlm-ta): Blood Cancer J
                Journal ID (iso-abbrev): Blood Cancer J
                Title: Blood Cancer Journal
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2044-5385
                Publication date (Electronic): 22 February 2021
                Publication date PMC-release: 22 February 2021
                Publication date Collection: February 2021
                Volume: 11
                Issue: 2
                Electronic Location Identifier: 41
                Affiliations
                GRID grid.240145.6, ISNI 0000 0001 2291 4776, Department of Leukemia, , MD Anderson Cancer Center, ; Houston, TX USA
                Author information
                https://orcid.org/http://orcid.org/0000-0002-1908-3307
                https://orcid.org/http://orcid.org/0000-0002-9892-9832
                https://orcid.org/http://orcid.org/0000-0001-9003-0390
                https://orcid.org/http://orcid.org/0000-0001-7103-373X
                https://orcid.org/http://orcid.org/0000-0001-7679-6453
                https://orcid.org/http://orcid.org/0000-0002-3631-2482
                https://orcid.org/http://orcid.org/0000-0002-9347-2212
                Article
                Publisher ID: 425
                DOI: 10.1038/s41408-021-00425-3
                PMC ID: 7900255
                PubMed ID: 33619261
                SO-VID: e148b700-064b-4ea8-a43a-8e8e9529f40b
                Copyright statement: © The Author(s) 2021
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 21 October 2020
                Date revision received : 14 December 2020
                Date accepted : 18 January 2021
                Funding
                Funded by: MD Anderson Leukemia SPORE CA100632 Cancer Center Support Grant (CCSG) P30CA016672 Charif Souki Cancer Research Grant
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prognosis,health services
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prognosis, health services

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