An In Silico Analysis of CRISPR Therapy Targeting NPM1 Mutations in Acute Myeloid Leukemia
Publication Date : Sep-16-2025
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Abstract :
Acute myeloid leukemia (AML) is a blood cancer typically affecting myeloid cells in the bone marrow. It is most common in adults and is characterized by its aggressive nature and relatively high likelihood of relapse. One of the most frequent mutations observed in patients with AML is a mutated NPM1 gene, which may lead to aberrant cytoplasmic localization of the NPM1 protein. FLT3 mutations are also commonly linked to NPM1 mutations and often signify poor prognosis in individuals with AML. Though research is being done into the prevention of these mutations, there are still very few treatments specifically targeting NPM1-mutated AML. In this study, a hypothetical CRISPR/Cas9 gen editing strategy was proposed as a possible path to study approaches for therapy to target mutant NPM1 genes and subsequent mutations in FLT3. Techniques such as transmembrane domain analysis and multiple protein alignment were used to explore protein characteristics such as localization and amino acid conservation patterns. A hypothetical CRISPR/Cas9 gene editing, polymerase chain reaction (PCR), and gel electrophoresis were simulated in exon 12 (a region commonly associated with NPM1 mutations) to propose a future research path for investigating the effects of mutations in the NPM1 gene. The goal was to generate a strategy to investigate whether a precise gRNA applied as a CRISPR/Cas9 gene editing could be a potential solution to limit the effect of NPM1 and FLT3 mutated proteins, therefore decreasing the development and severity of AML in the future.
