مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Designing a personalized gene therapy pathway for AML based on the functional assessment of NPM1 and the elimination of mutagenic elements
Designing a personalized gene therapy pathway for AML based on the functional assessment of NPM1 and the elimination of mutagenic elements
Dr Ali goudarzi,1,*Moein kavousi,2ِDr. Mohammad Mahdi Eslami,3Dr. Reza Mirlohi,4
2. Islamic Azad University, Islamshahr Branch 3. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran 4. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran
Introduction: Cancers represent a diverse group of genetic and metabolic disorders characterized by uncontrolled cell proliferation and dependence on both intrinsic mutations and extrinsic factors such as the tumor microenvironment and inflammation. Among them, Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy arising from hematopoietic stem or progenitor cells that acquire molecular abnormalities, leading to impaired differentiation and bone marrow failure. Despite advances in therapy, outcomes remain poor, particularly in relapsed or refractory cases. Cytokine-mediated activation of the JAK/STAT pathway has emerged as a key mechanism underlying therapeutic resistance, especially against CAR T cell–based immunotherapy. This study focuses on elucidating the molecular mechanisms of AML resistance and exploring the therapeutic potential of targeting the JAK/STAT signaling axis.
Methods: In this study, the MegaGene 4 bioinformatics platform was employed to design and model gene therapy strategies targeting the selected gene. Genomic and proteomic data, including coding sequences and regulatory elements, were analyzed to construct optimized gene therapy vectors and simulate associated molecular pathways. The integrative computational framework enabled predictive modeling of therapeutic efficacy, forming the basis for future experimental validation.
Results: FLT3-shRNA and CRISPR-NPM1 effectively suppressed oncogenic pathways and corrected AML mutations. AAV6-CD33-iCasp9 ensured safety control, while CRISPR-HSC showed strong potential for multi-gene and curative AML therapy.
Conclusion: In comparison with previous studies, FLT3-shRNA and CRISPR-NPM1 showed effective suppression of oncogenic pathways and correction of AML-related mutations.
AAV6-CD33-iCasp9 provided controlled safety, while CRISPR-HSC demonstrated potential for multi-gene and curative AML therapy.