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- W2301982004 abstract "Purpose: Recurrent gene mutations, chromosomal translocations, and acquired genomic copy number aberrations (aCNA) have been variously associated with acute myelogenous leukemia (AML) patient outcome. However, knowledge of the co-occurrence of such lesions and the relative influence of different types of genomic alterations on clinical outcomes in AML is still evolving. Experimental Design: We performed SNP 6.0 array-based genomic profiling of aCNA/copy neutral loss-of-heterozygosity (cnLOH) along with sequence analysis of 13 commonly mutated genes on purified leukemic blast DNA from 156 prospectively enrolled non-FAB-M3 AML patients across the clinical spectrum of de novo , secondary, and therapy-related AML. Results: TP53 and RUNX1 mutations are strongly associated with the presence of SNP-A–based aCNA/cnLOH, while FLT3 and NPM1 mutations are strongly associated with the absence of aCNA/cnLOH. The presence of mutations in RUNX1 , ASXL1 , and TP53 , elevated SNP-A–based genomic complexity, and specific recurrent aCNAs predicted failure to achieve a complete response to induction chemotherapy. The presence of ≥1 aCNA/cnLOH and higher thresholds predicted for poor long-term survival irrespective of TP53 status, and the presence of ≥1 aCNA/cnLOH added negative prognostic information to knowledge of mutations in TET2 , IDH1 , NPM1 , DNMT3A , and RUNX1 . Results of multivariate analyses support a dominant role for TP53 mutations and a role for elevated genomic complexity as predictors of short survival in AML. Conclusions: Integrated genomic profiling of a clinically relevant adult AML cohort identified genomic aberrations most associated with SNP-A–based genomic complexity, resistance to intensive induction therapies, and shortened overall survival. Identifying SNP-A–based lesions adds prognostic value to the status of several recurrently mutated genes. Clin Cancer Res; 1–12. ©2015 AACR." @default.
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- W2301982004 date "2015-06-01" @default.
- W2301982004 modified "2023-09-24" @default.
- W2301982004 title "Integrated Genomic Profiling, Therapy Response And Survival in Adult Acute Myelogenous Leukemia" @default.
- W2301982004 doi "https://doi.org/10.1016/j.clml.2015.04.044" @default.
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