Lavanyaa Gupta

Helios Scholar

Myeloproliferative neoplasms (MPNs) are a group of blood cancers characterized by the overproduction of one or more types of blood cells. Thirty percent (30%) of patients with chronic MPN will progress to secondary acute myeloid leukemia (sAML), an often life-threatening condition. This pilot study seeks to address an unmet clinical need by identifying novel structural variations (SVs) that could serve as predictive biomarkers, facilitating earlier detection of disease progression and enabling timely interventions to prevent the fatal advancement to sAML. Patient samples were selected from the Hematopoietic Stem Cell Biorepository, City of Hope. Short- and long-read whole genome sequencing data was generated for each sample using the Illumina NovaSeq6000 and the Oxford Nanopore Promethion, respectively. These data were merged and filtered using a publicly available tool, SURVIVOR, and custom Bash and RStudio scripts. Cleaned data files were then analyzed using custom allele counting scripts and Fisher’s Exact Test in RStudio. Our results include 102 statistically significant genomic regions (p-value < 0.05) including 8 highly significant results (p-value < 0.01). SVs were visually confirmed in the Integrated Genome Viewer (IGV) and biological insights for the top regions were investigated using University of California, Santa Cruz Genome Browser and Ensembl. Findings from our pilot study highlight the potential of SVs to improve prognostication and guide personalized treatment strategies in MPN patients. Future work includes: increasing sample size, replication of our results, and investigation of the genes and inter-genic regions where the SVs are mapping.