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- W4361953776 abstract "<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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 <i>de novo</i>, secondary, and therapy-related AML.</p><p><b>Results:</b> <i>TP53</i> and <i>RUNX1</i> mutations are strongly associated with the presence of SNP-A–based aCNA/cnLOH, while <i>FLT3</i> and <i>NPM1</i> mutations are strongly associated with the absence of aCNA/cnLOH. The presence of mutations in <i>RUNX1</i>, <i>ASXL1</i>, and <i>TP53</i>, 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 <i>TP53</i> status, and the presence of ≥1 aCNA/cnLOH added negative prognostic information to knowledge of mutations in <i>TET2</i>, <i>IDH1</i>, <i>NPM1</i>, <i>DNMT3A</i>, and <i>RUNX1</i>. Results of multivariate analyses support a dominant role for <i>TP53</i> mutations and a role for elevated genomic complexity as predictors of short survival in AML.</p><p><b>Conclusions:</b> 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. <i>Clin Cancer Res; 21(9); 2045–56. ©2015 AACR</i>.</p></div>" @default.
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- W4361953776 date "2023-03-31" @default.
- W4361953776 modified "2023-09-26" @default.
- W4361953776 title "Data from Integrated Genomic Profiling, Therapy Response, and Survival in Adult Acute Myelogenous Leukemia" @default.
- W4361953776 doi "https://doi.org/10.1158/1078-0432.c.6524256.v1" @default.
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