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Acute myeloid leukemia

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.

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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.

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Correspondence to H-A Hou or H-F Tien.

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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

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