This project aims to sequence an unparalleled number of cases of de novo Acute Myeloid Leukemia (AML) and Down Syndrome AML (DS-AML), to establish a database comprised of genomic and transcriptome information which can be interrogated for both somatic and germline variants. Identification of the somatic variants will provide valuable data on the potential genes and pathways that can be targeted for therapeutic purposes. In addition, interrogation of the host's constitutional genome may yield valuable information about potential germline variants that, in combination with the somatic data, might provide a more informed approach to patient care. For those patients with predisposition mutations, chemotherapy alone might not be adequate for cure, and stem cell transplantation might be required. Also, those who might be at high risk of adverse secondary events (cardiac complications, secondary malignancies, etc.) can be identified early and their therapy can be tailored to minimize anticipated complications. Thus, we propose that the optimum outcome can only be obtained through comprehensive interrogation of the somatic and germline genomes to fully annotate the genomic makeup of the leukemia and its host. Knowing the genomic and transcriptomic makeup of these patients, along with a full complement of clinical characteristics for this cohort, will be critical for making strong correlations which may aid in therapeutic development for future patients. The de novo AML, DS-AML, and Acute Promyelocytic Leukemia (APL) cases were all collected through clinical protocols conducted by the <a href="https://www.childrensoncologygroup.org/">Children's Oncology Group (COG)</a>. In addition to funding from the <a href="https://www.commonfund.nih.gov/KidsFirst">Gabriella Miller Kids First Pediatric Research Program</a>, the DS-AML cohort was specifically funded by the Lifespan to Understand Down syndrome (INCLUDE) Project.

Gabriella Miller Kids First Pediatric Research Program in Germline and Somatic Variants in Myeloid Malignancies in Children

The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions