Summary
Research on mutation mechanisms leading to malignant transformation and chemotherapy resistance in leukemia, including chromosomal translocation and point mutations, with a focus on novel mutation signatures.
Mutation Mechanisms Leading to Malignant Transformation, Including Chromosomal Translocation and Point Mutations
US · IL
NIH
grant
open
#nih-1ZIASC010379-25
What they want
The project involves generating T-ALL cell lines and chemotherapy-resistant derivatives, assaying for acquired single nucleotide variants (SNV), copy number aberrations (CNA), and RNA transcription changes to identify events in developing chemotherapy resistance. It includes developing a novel in vitro assay (GEMINI) to study a newly identified mutation signature, investigating its components (Trp53, cell division rate), and studying mutagenic properties of both novel and FDA approved azanucleosides. More recently, the project has identified and characterized recurrent mutations in mitochondrial DNA (mtDNA) produced after treatment with specific chemotherapy agents, comparing their features to nuclear DNA mutations.
Deliverables
- Submit a manuscript detailing findings on Dck inactivation and novel mutation signature in late FY2025
- Published one manuscript documenting azanucleoside mutations in FY2025 (PMID: 40681875)
- A second manuscript highlighting mechanisms of azanucleoside mutations (in press)
- Submit a manuscript describing mtDNA mutation findings in late FY2025
Technical requirements
- Assayed for acquired single nucleotide variants (SNV)
- Assayed for copy number aberrations (CNA)
- Assayed for RNA transcription changes
- Novel in vitro assay (GEMINI)
