Genetic alterations and their clinical implications in older patients with acute myeloid leukemia

ABSTRACT A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies

regarding the impact of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and

those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of _PTPN11_, _NPM1_, _RUNX1_, _ASXL1_, _TET2_,

_DNMT3A_ and _TP53_ mutations but a lower frequency of _WT1_ mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that

_DNMT3A_ and _TP53_ mutations were independent poor prognostic factors among the elderly, while _NPM1_ mutation in the absence of _FLT3_/ITD was an independent favorable prognostic factor.

Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic

alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the

outcome of older patients with poor prognosis under current treatment modalities. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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TRAJECTORIES IN NON-INTENSIVELY TREATED ELDERLY ACUTE MYELOID LEUKEMIA PATIENTS Article Open access 17 August 2023 POOR PROGNOSTIC IMPLICATIONS OF MYELODYSPLASIA-RELATED MUTATIONS IN BOTH

OLDER AND YOUNGER PATIENTS WITH _DE NOVO_ AML Article Open access 04 January 2023 IMPACT OF GENE ALTERATIONS ON CLINICAL OUTCOME IN YOUNG ADULTS WITH MYELODYSPLASTIC SYNDROMES Article Open

access 14 February 2023 REFERENCES * Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF _et al_(eds). _SEER Cancer Statistics Review, 1975-2010_ 2013 National Cancer

Institute: Bethesda, MD, USA, Available at: http://seer.cancer.gov/csr/1975_2010/. Google Scholar  * Burnett A, Wetzler M, Lowenberg B . Therapeutic advances in acute myeloid leukemia. _J

Clin Oncol_ 2011; 29: 487–494. Article  PubMed  Google Scholar  * Lowenberg B, Downing JR, Burnett A . Acute myeloid leukemia. _N Engl J Med_ 1999; 341: 1051–1062. Article  CAS  PubMed 

Google Scholar  * Hiddemann W, Kern W, Schoch C, Fonatsch C, Heinecke A, Wormann B _et al_. Management of acute myeloid leukemia in elderly patients. _J Clin Oncol_ 1999; 17: 3569–3576.

Article  CAS  PubMed  Google Scholar  * Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE _et al_. Age and acute myeloid leukemia. _Blood_ 2006; 107: 3481–3485. Article 

CAS  PubMed  PubMed Central  Google Scholar  * Erba HP . Prognostic factors in elderly patients with AML and the implications for treatment. _Hematology Am Soc Hematol Educ Program_ 2007,

420–428. Article  Google Scholar  * Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK _et al_. Diagnosis and management of acute myeloid leukemia in adults: recommendations

from an international expert panel, on behalf of the European LeukemiaNet. _Blood_ 2010; 115: 453–474. Article  PubMed  Google Scholar  * Grimwade D, Hills RK, Moorman AV, Walker H, Chatters

S, Goldstone AH _et al_. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876

younger adult patients treated in the United Kingdom Medical Research Council trials. _Blood_ 2010; 116: 354–365. Article  CAS  PubMed  Google Scholar  * Hou HA, Lin CC, Chou WC, Liu CY,

Chen CY, Tang JL _et al_. Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia. _Leukemia_ 2014; 28: 50–58.

Article  CAS  PubMed  Google Scholar  * Schlenk RF, Dohner K, Krauter J, Frohling S, Corbacioglu A, Bullinger L _et al_. Mutations and treatment outcome in cytogenetically normal acute

myeloid leukemia. _N Engl J Med_ 2008; 358: 1909–1918. Article  CAS  PubMed  Google Scholar  * Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE _et al_. DNMT3A mutations in

acute myeloid leukemia. _N Engl J Med_ 2010; 363: 2424–2433. Article  CAS  PubMed  PubMed Central  Google Scholar  * Falini B, Mecucci C, Tiacci E, Alcalay M, Rosati R, Pasqualucci L _et

al_. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. _N Engl J Med_ 2005; 352: 254–266. Article  CAS  PubMed  Google Scholar  * Schnittger S, Schoch C, Dugas

M, Kern W, Staib P, Wuchter C _et al_. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG

study and usefulness as a marker for the detection of minimal residual disease. _Blood_ 2002; 100: 59–66. Article  CAS  PubMed  Google Scholar  * Metzeler KH, Becker H, Maharry K, Radmacher

MD, Kohlschmidt J, Mrozek K _et al_. ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category.

_Blood_ 2011; 118: 6920–6929. Article  CAS  PubMed  PubMed Central  Google Scholar  * Mendler JH, Maharry K, Radmacher MD, Mrozek K, Becker H, Metzeler KH _et al_. RUNX1 mutations are

associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures. _J Clin Oncol_ 2012;

30: 3109–3118. Article  PubMed  PubMed Central  Google Scholar  * Paschka P, Marcucci G, Ruppert AS, Whitman SP, Mrozek K, Maharry K _et al_. Wilms' tumor 1 gene mutations independently

predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study. _J Clin Oncol_ 2008; 26: 4595–4602. Article  CAS  PubMed  PubMed

Central  Google Scholar  * Tang JL, Hou HA, Chen CY, Liu CY, Chou WC, Tseng MH _et al_. AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication

and interaction with other gene alterations. _Blood_ 2009; 114: 5352–5361. Article  CAS  PubMed  Google Scholar  * Green CL, Evans CM, Zhao L, Hills RK, Burnett AK, Linch DC _et al_. The

prognostic significance of IDH2 mutations in AML depends on the location of the mutation. _Blood_ 2011; 118: 409–412. Article  CAS  PubMed  Google Scholar  * Marcucci G, Maharry K, Wu YZ,

Radmacher MD, Mrozek K, Margeson D _et al_. IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia

Group B study. _J Clin Oncol_ 2010; 28: 2348–2355. Article  CAS  PubMed  PubMed Central  Google Scholar  * Hou HA, Kuo YY, Liu CY, Chou WC, Lee MC, Chen CY _et al_. DNMT3A mutations in acute

myeloid leukemia: stability during disease evolution and clinical implications. _Blood_ 2012; 119: 559–568. Article  CAS  PubMed  Google Scholar  * Hou HA, Tien HF . Mutations in epigenetic

modifiers in acute myeloid leukemia and their clinical utility. _Expert Rev Hematol_ e-pub ahead of print 9 February 2016, 1–23. * Chou SC, Tang JL, Hou HA, Chou WC, Hu FC, Chen CY _et al_.

Prognostic implication of gene mutations on overall survival in the adult acute myeloid leukemia patients receiving or not receiving allogeneic hematopoietic stem cell transplantations.

_Leuk Res_ 2014; 38: 1278–1284. Article  CAS  PubMed  Google Scholar  * Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR _et al_. Proposed revised criteria for the

classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. _Ann Intern Med_ 1985; 103: 620–625. Article  CAS  PubMed  Google Scholar  * Tien HF,

Wang CH, Lin MT, Lee FY, Liu MC, Chuang SM _et al_. Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study

of 235 Chinese patients in Taiwan. _Cancer Genet Cytogenet_ 1995; 84: 60–68. Article  CAS  PubMed  Google Scholar  * Chou WC, Hou HA, Liu CY, Chen CY, Lin LI, Huang YN _et al_. Sensitive

measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides prognostic information. _Ann Oncol_ 2011; 22: 696–704. Article  PubMed  Google Scholar  *

Bacher U, Haferlach C, Kern W, Haferlach T, Schnittger S . Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients. _Blood_ 2008; 111:

2527–2537. Article  CAS  PubMed  Google Scholar  * Hou HA, Kuo YY, Tang JL, Chou WC, Yao M, Lai YJ _et al_. Clinical implications of the SETBP1 mutation in patients with primary

myelodysplastic syndrome and its stability during disease progression. _Am J Hematol_ 2014; 89: 181–186. Article  CAS  PubMed  Google Scholar  * Hou HA, Chou WC, Lin LI, Chen CY, Tang JL,

Tseng MH _et al_. Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD. _Leukemia_ 2008;

22: 1075–1078. Article  CAS  PubMed  Google Scholar  * Lin LI, Chen CY, Lin DT, Tsay W, Tang JL, Yeh YC _et al_. Characterization of CEBPA mutations in acute myeloid leukemia: most patients

with CEBPA mutations have biallelic mutations and show a distinct immunophenotype of the leukemic cells. _Clin Cancer Res_ 2005; 11: 1372–1379. Article  CAS  PubMed  Google Scholar  * Hou

HA, Huang TC, Lin LI, Liu CY, Chen CY, Chou WC _et al_. WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its

incorporation into a survival scoring system. _Blood_ 2010; 115: 5222–5231. Article  CAS  PubMed  Google Scholar  * Hou HA, Chou WC, Kuo YY, Liu CY, Lin LI, Tseng MH _et al_. TP53 mutations

in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution. _Blood Cancer J_ 2015; 5: e331. Article  PubMed  PubMed Central 

Google Scholar  * Thol F, Bollin R, Gehlhaar M, Walter C, Dugas M, Suchanek KJ _et al_. Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications.

_Blood_ 2014; 123: 914–920. Article  CAS  PubMed  Google Scholar  * Shiah HS, Kuo YY, Tang JL, Huang SY, Yao M, Tsay W _et al_. Clinical and biological implications of partial tandem

duplication of the MLL gene in acute myeloid leukemia without chromosomal abnormalities at 11q23. _Leukemia_ 2002; 16: 196–202. Article  CAS  PubMed  Google Scholar  * Chen TC, Hou HA, Chou

WC, Tang JL, Kuo YY, Chen CY _et al_. Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome. _Blood

Cancer J_ 2014; 4: e177. Article  PubMed  PubMed Central  Google Scholar  * Lin CC, Hou HA, Chou WC, Kuo YY, Liu CY, Chen CY _et al_. IDH mutations are closely associated with mutations of

DNMT3A, ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution. _Am J Hematol_ 2014; 89: 137–144. Article  CAS  PubMed  Google Scholar  * Chou WC,

Lei WC, Ko BS, Hou HA, Chen CY, Tang JL _et al_. The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia. _Leukemia_ 2011;

25: 246–253. Article  CAS  PubMed  Google Scholar  * Chou WC, Chou SC, Liu CY, Chen CY, Hou HA, Kuo YY _et al_. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia

patients with intermediate-risk cytogenetics. _Blood_ 2011; 118: 3803–3810. Article  CAS  PubMed  Google Scholar  * Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH _et

al_. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in

Acute Myeloid Leukemia. _J Clin Oncol_ 2003; 21: 4642–4649. Article  PubMed  Google Scholar  * Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G _et al_. The importance of

diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties.

_Blood_ 1998; 92: 2322–2333. CAS  PubMed  Google Scholar  * Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL _et al_. Acute myeloid leukemia ontogeny is defined by distinct

somatic mutations. _Blood_ 2015; 125: 1367–1376. Article  CAS  PubMed  PubMed Central  Google Scholar  * Hou HA, Liu CY, Kuo YY, Chou WC, Tsai CH, Lin CC _et al_. Splicing factor mutations

predict poor prognosis in patients with de novo acute myeloid leukemia. _Oncotarget_ e-pub ahead of print 24 January 2016; doi:10.18632/oncotarget.7000. * Mengis C, Aebi S, Tobler A, Dahler

W, Fey MF . Assessment of differences in patient populations selected for excluded from participation in clinical phase III acute myelogenous leukemia trials. _J Clin Oncol_ 2003; 21:

3933–3939. Article  PubMed  Google Scholar  * Keating MJ, Smith TL, Kantarjian H, Cork A, Walters R, Trujillo JM _et al_. Cytogenetic pattern in acute myelogenous leukemia: a major

reproducible determinant of outcome. _Leukemia_ 1988; 2: 403–412. CAS  PubMed  Google Scholar  * Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A _et al_. Karyotypic

analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. _Blood_ 2000; 96:

4075–4083. CAS  PubMed  Google Scholar  * Kihara R, Nagata Y, Kiyoi H, Kato T, Yamamoto E, Suzuki K _et al_. Comprehensive analysis of genetic alterations and their prognostic impacts in

adult acute myeloid leukemia patients. _Leukemia_ 2014; 28: 1586–1595. Article  CAS  PubMed  Google Scholar  * Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J _et al_.

Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. _N Engl J Med_ 2012; 366: 1079–1089. Article  CAS  PubMed  PubMed Central  Google Scholar  * Becker H,

Marcucci G, Maharry K, Radmacher MD, Mrozek K, Margeson D _et al_. Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a

Cancer and Leukemia Group B study. _Blood_ 2010; 116: 788–792. Article  CAS  PubMed  PubMed Central  Google Scholar  * Stirewalt DL, Kopecky KJ, Meshinchi S, Appelbaum FR, Slovak ML, Willman

CL _et al_. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. _Blood_ 2001; 97: 3589–3595. Article  CAS  PubMed  Google Scholar  * Becker H, Marcucci G, Maharry

K, Radmacher MD, Mrozek K, Margeson D _et al_. Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated

gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study. _J Clin Oncol_ 2010; 28: 596–604. Article  CAS  PubMed  Google Scholar  * Ostronoff F, Othus M, Lazenby M,

Estey E, Appelbaum FR, Evans A _et al_. Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and

UK National Cancer Research Institute/Medical Research Council report. _J Clin Oncol_ 2015; 33: 1157–1164. Article  PubMed  PubMed Central  Google Scholar  * Kantarjian H, O'Brien S,

Cortes J, Giles F, Faderl S, Jabbour E _et al_. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome:

predictive prognostic models for outcome. _Cancer_ 2006; 106: 1090–1098. Article  PubMed  Google Scholar  * Oran B, Weisdorf DJ . Survival for older patients with acute myeloid leukemia: a

population-based study. _Haematologica_ 2012; 97: 1916–1924. Article  PubMed  PubMed Central  Google Scholar  * Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D _et

al_. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. _Blood_ 2009; 113: 4179–4187. Article  CAS  PubMed  Google

Scholar  * Juliusson G . Older patients with acute myeloid leukemia benefit from intensive chemotherapy: an update from the Swedish Acute Leukemia Registry. _Clin Lymphoma Myeloma Leuk_

2011; 11 (Suppl 1): S54–S59. Article  PubMed  Google Scholar  * Schoch C, Kern W, Krawitz P, Dugas M, Schnittger S, Haferlach T _et al_. Dependence of age-specific incidence of acute myeloid

leukemia on karyotype. _Blood_ 2001; 98: 3500. Article  CAS  PubMed  Google Scholar  * Schoch C, Kern W, Schnittger S, Buchner T, Hiddemann W, Haferlach T . The influence of age on

prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. _Haematologica_ 2004; 89: 1082–1090. PubMed  Google Scholar  * Moorman AV, Roman E, Willett EV, Dovey

GJ, Cartwright RA, Morgan GJ . Karyotype and age in acute myeloid leukemia. Are they linked? _Cancer Genet Cytogenet_ 2001; 126: 155–161. Article  CAS  PubMed  Google Scholar  * Appelbaum

FR, Kopecky KJ, Tallman MS, Slovak ML, Gundacker HM, Kim HT _et al_. The clinical spectrum of adult acute myeloid leukaemia associated with core binding factor translocations. _Br J

Haematol_ 2006; 135: 165–173. Article  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This work was partially sponsored by grants MOST

100-2628-B-002-003-MY3,103-2628-B-002-008-MY3, 103-2923-B-002 -001 and 104-2314-B-002-128-MY4 from the Ministry of Science and Technology (Taiwan), MOHW105-TDU-B-211-134005 from the Ministry

of Health and Welfare (Taiwan), NTUH 102P06, from the Department of Medical Research, National Taiwan University Hospital, and Taiwan Health Foundation. We would like to acknowledge the

service provided by the DNA Sequencing Core of the First Core Laboratory, National Taiwan University College of Medicine. AUTHOR CONTRIBUTIONS C-HT was responsible for data management and

interpretation, statistical analysis and manuscript writing; H-AH was responsible for study design and plan, literature collection, data management and interpretation, statistical analysis

and manuscript writing; C-YL was responsible for statistical analysis and interpretation of the statistical findings; Y-YK, L-IL was responsible for mutation analysis and interpretation;

C-YC, W-CC, M-Y, S-YH, J-LT, B-SK, S-CH, C-TL, C-CL, S-JW, S-CC, WT and Y-CC contributed patient samples and clinical data; M-HT, C-FH, Y-CC, C-YL, F-YL and M-CL performed the gene mutation

and chromosomal studies and H-FT designed and coordinated the study over the entire period and wrote the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Hematology,

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan C-H Tsai, H-A Hou, J-L Tang, C-C Lin, W-C Chou, M-H Tseng, Y-C Chiang, W Tsay, M Yao, C-C Li, S-Y Huang, 

B-S Ko, C-Y Chen, C-T Lin, S-J Wu & H-F Tien * Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan C-H Tsai & C-C Lin * Tai-Cheng

Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan C-H Tsai, J-L Tang, C-C Li & C-T Lin * Biostatistics Consulting Laboratory, School of Nursing, National Taipei

University of Nursing and Health Sciences, Taipei, Taiwan C-Y Liu * Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan C-C Lin, W-C Chou & S-C Hsu *

Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan Y-Y Kuo * Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan M-C Liu

 & C-W Liu * Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan L-I Lin Authors * C-H Tsai View author

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and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tsai, CH., Hou, HA., Tang, JL. _et al._ Genetic alterations and their clinical implications in older patients with acute myeloid

leukemia. _Leukemia_ 30, 1485–1492 (2016). https://doi.org/10.1038/leu.2016.65 Download citation * Received: 10 October 2015 * Revised: 20 February 2016 * Accepted: 25 February 2016 *

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