DNA Analysis of Tumor Tissue From Patients With Acute Myeloid Leukemia

• Nucleophosmin exon 12 mutation-related normal cytogenetics leukemia (NCL) has a specific genetic and epigenetic profile [ Designated as safety issue: No ]
  
• Relatedness on a per-gene basis of cross-platform data [ Designated as safety issue: No ]
  
• Ability of supervised clustering to distinguish subgroups according to clinical prognostic and biomarker indicators [ Designated as safety issue: No ]
  
• Ability of unsupervised clustering to identify subgroups of NCL patients [ Designated as safety issue: No ]
  
• Relative power of each platform mentioned above vs the integrated platforms [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine gene expression, genome integrity, cytosine methylation, and chromatin structure in patients with normal cytogenetics leukemia (NCL) acute myeloid leukemia.
• Determine whether NCL can be deconstructed into specific disease entities by analysis of the integrated genomic and epigenomic datasets using supervised and unsupervised methods in these patients.
• Identify the gene pathways that define NCL subtypes and molecular targets for validation in preclinical and clinical trials for these patients.
• Determine whether integrated analysis provides markers of prognostic and therapeutic response that accurately predicts clinical outcome and can be used to select patients for risk-stratified therapeutic trials.

OUTLINE: This is a pilot, multicenter study.

Samples are analyzed to assess array comparative genomic hybridization using polymerase chain reaction (PCR) and fluorescent in situ hybridization; chromatin immunoprecipitations (chip) using PCR; Hpa II tiny fragment enrichment by ligation-mediated PCR (HELP) using DNA methylation analysis; and gene expression profiling.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study.