Functional Genomic Landscape of Acute Myeloid Leukemia

The implementation of targeted therapies for acute myeloid leukemia has been challenged by complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. The initial findings from the Beat AML program were from a cohort of 672 tumor specimens collected from 562 patients. Additional patients have been added in subsequent versions. We assessed these specimens using whole exome sequencing, RNA-sequencing, and ex vivo drug sensitivity analyses. Our data reveal novel mutational events not previously detected in AML. We show association of drug response with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA-sequencing also revealed gene expression signatures, which predict a role of specific gene networks in drug response. Collectively, this report offers a dataset, accessible by the Beat AML data viewer (www.vizome.org), that can be leveraged to address clinical, genomic, transcriptomic, and functional inquiries into the biology of AML.

• Study Weblinks:
  • Vizome
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Longitudinal
• Total number of consented subjects: 829
• Subject Sample Telemetry Report (SSTR)

• BioProject
• Sequence Read Archive
• BioSample
• Clinical Trials
  • NCT01728402

All patients with a presumed diagnosis of AML were eligible for specimen collection on this study (listed at clinicaltrails.gov - NCT01728402).

Samples were obtained according to the Declaration of Helsinki. All patients gave consent to participate in this study, which had the approval and guidance of the institutional review boards at Oregon Health & Science University (OHSU), University of Utah, University of Texas Medical Center (UT Southwestern), Stanford University, University of Miami, University of Colorado, University of Florida, National Institutes of Health (NIH), Fox Chase Cancer Center and University of Kansas (KUMC). Samples were sent to the coordinating center (OHSU; IRB#9570) where they were coded and processed.

• Primary Phenotype: Leukemia, Myeloid, Acute

• Principal Investigator
  • Jeffrey W. Tyner, PhD. Oregon Health and Science University, Knight Cancer Institute, Portland, OR, USA.
• Funding Sources
  • The Leukemia and Lymphoma Society, Beat AML, Rye Brook, NY, USA.
  • 1U54CA224019. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • 1U01CA217862. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • 3P30CA069533-18S5. National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.