Gene Mutations As Emerging Biomarkers and Therapeutic Targets for Relapsed Acute Myeloid Leukemia

Overview

Journal Front Pharmacol

Date 2017 Dec 23

PMID 29270125

Citations 7

Authors

Habsah Aziz

Chow Y Ping

Hamidah Alias

Nurul-Syakima Ab Mutalib

Rahman Jamal

Affiliations

Soon will be listed here.

Abstract

It is believed that there are key differences in the genomic profile between adult and childhood acute myeloid leukemia (AML). Relapse is the significant contributor of mortality in patients with AML and remains as the leading cause of cancer death among children, posing great challenges in the treatment of AML. The knowledge about the genomic lesions in childhood AML is still premature as most genomic events defined in children were derived from adult cohorts. However, the emerging technologies of next generation sequencing have narrowed the gap of knowledge in the biology of AML by the detection of gene mutations for each sub-type which have led to the improvement in terms of prognostication as well as the use of targeted therapies. In this review, we describe the recent understanding of the genomic landscape including the prevalence of mutation, prognostic impact, and targeted therapies that will provide an insight into the pathogenesis of AML relapse in both adult and childhood cases.

Citing Articles

Optimizing NK Cell-Based Immunotherapy in Myeloid Leukemia: Abrogating an Immunosuppressive Microenvironment.

Kaweme N, Zhou F Front Immunol. 2021; 12:683381.

PMID: 34220833 PMC: 8247591. DOI: 10.3389/fimmu.2021.683381.

Long Noncoding RNAs in Acute Myeloid Leukemia: Functional Characterization and Clinical Relevance.

Gourvest M, Brousset P, Bousquet M Cancers (Basel). 2019; 11(11).

PMID: 31653018 PMC: 6896193. DOI: 10.3390/cancers11111638.

A six-gene-based prognostic model predicts complete remission and overall survival in childhood acute myeloid leukemia.

Zhang N, Chen Y, Lou S, Shen Y, Deng J Onco Targets Ther. 2019; 12:6591-6604.

PMID: 31496748 PMC: 6701647. DOI: 10.2147/OTT.S218928.

Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine.

Tang L, Sun G, Zhang T, Wu D, Zhou J, Ma B Cancer Cell Int. 2019; 19:177.

PMID: 31333331 PMC: 6617691. DOI: 10.1186/s12935-019-0894-y.

Long Non-Coding RNA and Acute Leukemia.

Cruz-Miranda G, Hidalgo-Miranda A, Barcenas-Lopez D, Nunez-Enriquez J, Ramirez-Bello J, Mejia-Arangure J Int J Mol Sci. 2019; 20(3).

PMID: 30744139 PMC: 6387068. DOI: 10.3390/ijms20030735.

References

Ley T, Ding L, Walter M, McLellan M, Lamprecht T, Larson D . DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010; 363(25):2424-33. PMC: 3201818. DOI: 10.1056/NEJMoa1005143. View

Markova J, Michkova P, Burckova K, Brezinova J, Michalova K, Dohnalova A . Prognostic impact of DNMT3A mutations in patients with intermediate cytogenetic risk profile acute myeloid leukemia. Eur J Haematol. 2011; 88(2):128-35. DOI: 10.1111/j.1600-0609.2011.01716.x. View

Ofran Y, Rowe J . Genetic profiling in acute myeloid leukaemia--where are we and what is its role in patient management. Br J Haematol. 2012; 160(3):303-20. DOI: 10.1111/bjh.12135. View

Cao Q, Gearhart M, Gery S, Shojaee S, Yang H, Sun H . BCOR regulates myeloid cell proliferation and differentiation. Leukemia. 2016; 30(5):1155-65. PMC: 5131645. DOI: 10.1038/leu.2016.2. View

Grossmann V, Tiacci E, Holmes A, Kohlmann A, Martelli M, Kern W . Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype. Blood. 2011; 118(23):6153-63. DOI: 10.1182/blood-2011-07-365320. View

Renneville A, Boissel N, Zurawski V, Llopis L, Biggio V, Nibourel O . Wilms tumor 1 gene mutations are associated with a higher risk of recurrence in young adults with acute myeloid leukemia: a study from the Acute Leukemia French Association. Cancer. 2009; 115(16):3719-27. DOI: 10.1002/cncr.24442. View

Kawahara M, Pandolfi A, Bartholdy B, Barreyro L, Will B, Roth M . H2.0-like homeobox regulates early hematopoiesis and promotes acute myeloid leukemia. Cancer Cell. 2012; 22(2):194-208. PMC: 3422691. DOI: 10.1016/j.ccr.2012.06.027. View

Dohner H, Weisdorf D, Bloomfield C . Acute Myeloid Leukemia. N Engl J Med. 2015; 373(12):1136-52. DOI: 10.1056/NEJMra1406184. View

Stein E, Tallman M . Emerging therapeutic drugs for AML. Blood. 2015; 127(1):71-8. PMC: 4915807. DOI: 10.1182/blood-2015-07-604538. View

10.

Paschka P, Schlenk R, Gaidzik V, Habdank M, Kronke J, Bullinger L . IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol. 2010; 28(22):3636-43. DOI: 10.1200/JCO.2010.28.3762. View

11.

Shih L, Huang C, Wu J, Lin T, Dunn P, Wang P . Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples from 108 adult patients at diagnosis and relapse. Blood. 2002; 100(7):2387-92. DOI: 10.1182/blood-2002-01-0195. View

12.

Zhang H, Mi J, Fang H, Wang Z, Wang C, Wu L . Preferential eradication of acute myelogenous leukemia stem cells by fenretinide. Proc Natl Acad Sci U S A. 2013; 110(14):5606-11. PMC: 3619353. DOI: 10.1073/pnas.1302352110. View

13.

Martelli M, Sportoletti P, Tiacci E, Martelli M, Falini B . Mutational landscape of AML with normal cytogenetics: biological and clinical implications. Blood Rev. 2012; 27(1):13-22. DOI: 10.1016/j.blre.2012.11.001. View

14.

Bacher U, Haferlach T, Schoch C, Kern W, Schnittger S . Implications of NRAS mutations in AML: a study of 2502 patients. Blood. 2006; 107(10):3847-53. DOI: 10.1182/blood-2005-08-3522. View

15.

Schnittger S, Eder C, Jeromin S, Alpermann T, Fasan A, Grossmann V . ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome. Leukemia. 2012; 27(1):82-91. DOI: 10.1038/leu.2012.262. View

16.

Stein E, DiNardo C, Pollyea D, Fathi A, Roboz G, Altman J . Enasidenib in mutant relapsed or refractory acute myeloid leukemia. Blood. 2017; 130(6):722-731. PMC: 5572791. DOI: 10.1182/blood-2017-04-779405. View

17.

Kutny M, Alonzo T, Gamazon E, Gerbing R, Geraghty D, Lange B . Ethnic variation of TET2 SNP rs2454206 and association with clinical outcome in childhood AML: a report from the Children's Oncology Group. Leukemia. 2015; 29(12):2424-6. PMC: 4675677. DOI: 10.1038/leu.2015.171. View

18.

Dohner K, Schlenk R, Habdank M, Scholl C, Rucker F, Corbacioglu A . Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005; 106(12):3740-6. DOI: 10.1182/blood-2005-05-2164. View

19.

Shih A, Abdel-Wahab O, Patel J, Levine R . The role of mutations in epigenetic regulators in myeloid malignancies. Nat Rev Cancer. 2012; 12(9):599-612. DOI: 10.1038/nrc3343. View

20.

Brown P, Mcintyre E, Rau R, Meshinchi S, Lacayo N, Dahl G . The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood. 2007; 110(3):979-85. PMC: 1924773. DOI: 10.1182/blood-2007-02-076604. View