The controlled collection and processing of clinical specimens from patients with myeloid leukemia andmyelodysplastic syndrome continues to be a critical activity for the accurate, efficient, and comprehensiveacquisition of genomic data required for this program project. Similarly, a repository of quality controlled andstandardized tumor gene expression, gene copy number, and genotyping data corresponding to thesespecimens will continue to aid in elucidating the genomic basis of AMI. Procedural enhancements andoperation of microarray analytical platforms in a regulated laboratory environment will further prepare thistechnology for use in the context of molecular-based clinical trials for leukemia patients. Accordingly, thisCore has two Specific Aims:
Specific Aim 1 : We will collect, store, and process tissue specimens from all patients with adiagnosis of AML and MDS seen at this institution. We will include malignant cell populations from bonemarrow aspirates and peripheral blood as well as skin punch biopsy and buccal lavage specimensrepresenting non-malignant cell populations. Serum and plasma will be collected for future proteomicbiomarker studies. Specimens will be collected throughout each patient's disease course (initialpresentation, remission, relapse) and where appropriate, archival specimens from previous malignancies willbe retrieved. Specimens will be processed to cellular RNA, genomic DMA, whole genome amplified DNA,and protein extracts as required for each study. Cellular populations will also be viably frozen for futurexenograft studies. Particular attention to specimen procurement (e.g. rapid processing of leukemia cells topreserve transcript profiles) and quality control will be practiced.
Specific Aim 2 : Using the Affymetrix GeneChip platform, we will generate whole genomeexpression, copy number, and allelic loss data from all AML specimens collected during this study,under nationally accredited laboratory guidelines. Affymetrix whole genome (U133Plus2) and exonspecificexpression arrays will be used to generate quantitative and qualitative transcriptional profiles whilewhole genome genotyping (500K and 1M SNP) arrays will be used to simultaneously generate germlinegenotype data, somatic copy number change data, and allelic loss (LOH) data from tumor and non-malignantsample pairs. Emphasis will be place on developing new methods for rapid turnaround.
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