Integration of cytogenetic and molecular alterations in risk stratification of 318 patients with de novo non-M3 acute myeloid leukemia
Journal
Leukemia
Journal Volume
28
Journal Issue
1
Pages
50-58
Date Issued
2014
Author(s)
Liu C.-Y.
Lai Y.-J.
Tseng M.-H.
Huang C.-F.
Chiang Y.-C.
Lee F.-Y.
Kuo Y.-Y.
Lee M.-C.
Liu M.-C.
Liu C.-W.
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. ? 2014 Macmillan Publishers Limited.
SDGs
Other Subjects
asxl1 protein; CCAAT enhancer binding protein alpha; cytarabine; DNA methyltransferase 3A; Flt3 ligand; idarubicin; isocitrate dehydrogenase 2; nucleophosmin; protein; TET2 protein; transcription factor RUNX1; unclassified drug; WT1 protein; acute granulocytic leukemia; adolescent; adult; aged; article; cancer combination chemotherapy; cancer prognosis; cancer regression; cancer risk; cancer survival; cohort analysis; cytogenetics; drug dose increase; event free survival; female; gene mutation; genetic association; genetic risk; genotype; human; human cell; karyotype; major clinical study; male; middle aged; mutation rate; outcome assessment; overall survival; priority journal; recurrence free survival; treatment response; very elderly; young adult; Adolescent; Adult; Aged; Aged, 80 and over; Chromosome Aberrations; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Risk Factors; Young Adult
Type
journal article