Identification of -7/del7q Leukemia Specific Genetic Vulnerabilities
Anjali Kotamarthi, Biological Sciences, Health and Society, 2nd-Year
- Abstract
- -7/del7q Acute Myeloid Leukemia (AML) is a high-risk leukemia that accounts for about 8% of all AML patients, often resulting in a poorer prognosis as many generalized therapy methods such as chemotherapy are rendered ineffective. As the prognosis of myeloid leukemia patients remains poor, a need for targeted therapies which prove lethal to a select group of cells is needed in order to create a more effective and less toxic therapy. One approach is to identify essential genes on chromosome 7 which correlate to increased efficacy of particular drugs when expressed at haploinsufficient levels. Using previously published genome wide CRISPR-CAS9 knockout screen data conducted in AML cell lines, we identified 239 essential chromosome 7 genes in AML cell lines and further narrowed this list to 44 genes which can be targeted by a commercially available drug based on data collected from Drug-gene Interaction Database (DGIdb) and DrugBank. After identification, drug screening data performed in AML cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) database as well as drug screening data from AML patients in the BEAT AML database were utilized to verify if low expression of the target genes correlated with a difference in drug sensitivity through measured AUC values. Of the essential genes on chromosome 7 with a potential drug candidate, Bortezomib, a drug targeting proteasome subunit PSMA2, and Palbociclib which targets cyclin dependent kinase CDK6, hold potential of being more efficient in inhibiting cell proliferation in patients with -7/del7q karyotypes. These findings encourage the expansion of research for these drugs in relation to AML potentially through AML xenograft mouse models, and highlight the importance of characterizing genetics vulnerabilities in specific cancer types.
- Presented by
- Anjali Kotamarthi
- Research Mentors
- Prof. Megan McNerney, Pathology; Dr. Madhavi Senagolage, McNerney Lab
- Keywords
- Biological & Health Sciences


















































