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Acute Leukemias

Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia

Abstract

Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.

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Acknowledgements

This work was partially sponsored by Grants NSC 100-2314-B002-057-MY3, NSC 101-2325-B002-028 and NSC 100-2628-B-002003-MY3 from the National Science Council (Taiwan), DOH99-TD-C-111-001 from the Department of Health (Taiwan) and NTUH 102P06 and UN101-014 and 102-015 from the Department of Medical Research, National Taiwan University Hospital.

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Correspondence to H-F Tien.

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H-AH was responsible for study design and plan, literature collection, data management and interpretation, statistical analysis and manuscript writing; Y-YK, M-CL and L-IL were responsible for mutation analysis and interpretation; C-YL was responsible for statistical analysis and interpretation of the statistical findings; C-CL, C-YC, W-CC, M-Y, S-YH, J-LT, B-SK, S-CH, S-JW, WT and Y-CC contributed patient samples and clinical data; Y-JL, Y-CC, M-HT, C-FH, C-WL, F-YL and M-CL performed the gene mutation and chromosomal studies and H-FT planned, designed and coordinated the study over th entire period and wrote the manuscript.

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Hou, HA., Lin, CC., Chou, WC. et al. Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia. Leukemia 28, 50–58 (2014). https://doi.org/10.1038/leu.2013.236

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