IN SILICO ANALYSIS OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE POLYMORPHISMS AND THEIR POTENTIAL RELEVANCE IN ACUTE MYELOID LEUKEMIA
- 1Centro Universitário Nossa Senhora do Patrocínio, Itu, SP, Brasil
Abstract
Background: The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase involved in cellular proliferation, survival and differentiation. Although extensively studied in solid tumors, EGFR has also been detected at the protein level in a subset of acute myeloid leukemia (AML) samples, being functionally active in approximately 15% of patients. These findings raised interest in EGFR as a therapeutic target in AML, particularly regarding tyrosine kinase inhibitors such as erlotinib, although clinical results have been modest. Aim: To identify EGFR polymorphisms registered in public databases, classify their potential functional impact using an integrated prediction platform, and discuss their possible relevance in acute myeloid leukemia. Materials and methods: This computational study was based on in silico analysis. EGFR polymorphisms were identified through the dbSNP database (NCBI), and a minimum allele frequency filter (Minor Allele Frequency – MAF) between 0.1 and 1.0 was applied for variant selection. The selected variants were submitted to the PredictSNP2.0 platform, which integrates different functional prediction algorithms and classifies alterations as neutral or deleterious. Complementary data were obtained from ClinVar, Ensembl, OMIM, RegulomeDB and UCSC Genome Browser. Results: The initial search in dbSNP identified 85,415 variants associated with the EGFR gene. After the global allele frequency filter, 943 variants were selected for further analysis, of which 306 unique variants were submitted to the PredictSNP2.0 platform. Preliminary results showed that 34 variants were classified as deleterious by more than 50% of the integrated prediction tools. Notably, the rs2072454 polymorphism, in the C/A and C/G substitutions, was considered deleterious by 100% of the algorithms evaluated. Discussion: EGFR expression has been demonstrated in a subset of AML patients, with functional activation in approximately 15% of cases, indicating a possible role for this receptor in leukemic cell biology. Although erlotinib presented limited efficacy as a single agent in relapsed/refractory AML, preclinical evidence suggests off-target activity through pathways involved in AML differentiation. The consistent classification of common EGFR polymorphisms such as rs2072454 as deleterious suggests that structural alterations may compromise receptor function and influence the interaction with tyrosine kinase inhibitors, potentially affecting therapeutic response. Conclusion: The in silico analysis identified EGFR polymorphisms with high deleteriousness scores, including rs2072454, which deserve further investigation. These variants may produce structural changes capable of impairing receptor function and modulating the response to tyrosine kinase inhibitors, representing candidates for functional validation in the context of acute myeloid leukemia.
Related
- Evaluating Suspected Tumor Recurrence with Epidermal Growth Factor Receptor–Targeted [89Zr]Zr-Panitumumab PET/CT
- Factors Influencing the Treatment Response of Tetracyclines for Papulopustular Rash Induced by Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Retrospective Study.
- Amivantamab and lazertinib in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer with brain and leptomeningeal metastases: an editorial on efficacy, challenges in assessment, and future directions.
- Therapeutic Impact of Third-generation Tyrosine Kinase Inhibitors on Lung Squamous Cell Carcinoma with Epidermal Growth Factor Receptor Mutations: A Case Description and Systematic Literature Review
- Personalized Prediction of Venetoclax-Associated Tumor Lysis Syndrome in Acute Myeloid Leukemia Using Drug Exposure, Genetic Polymorphisms, and Clinical-Laboratory Characteristics.
BibTeX
@article{souza2026silico,
title = {{IN SILICO ANALYSIS OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE POLYMORPHISMS AND THEIR POTENTIAL RELEVANCE IN ACUTE MYELOID LEUKEMIA}},
author = {Amanda Rodrigues DE SOUZA and Agueda Aparecida AGUIAR DA SILVA and Vanessa Zanoni CARVALHAES and Larissa Teodoro RABI},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107602},
url = {https://doi.org/10.1016/j.htct.2026.107602},
note = {CC BY},
}
RIS
TY - JOUR
TI - IN SILICO ANALYSIS OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE POLYMORPHISMS AND THEIR POTENTIAL RELEVANCE IN ACUTE MYELOID LEUKEMIA
AU - Amanda Rodrigues DE SOUZA
AU - Agueda Aparecida AGUIAR DA SILVA
AU - Vanessa Zanoni CARVALHAES
AU - Larissa Teodoro RABI
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107602
UR - https://doi.org/10.1016/j.htct.2026.107602
AB - Background: The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase involved in cellular proliferation, survival and differentiation. Although extensively studied in solid tumors, EGFR has also been detected at the protein level in a subset of acute myeloid leukemia (AML) samples, being functionally active in approximately 15% of patients. These findings raised interest in EGFR as a therapeutic target in AML, particularly regarding tyrosine kinase inhibitors such as erlotinib, although clinical results have been modest. Aim: To identify EGFR polymorphisms registered in public databases, classify their potential functional impact using an integrated prediction platform, and discuss their possible relevance in acute myeloid leukemia. Materials and methods: This computational study was based on in silico analysis. EGFR polymorphisms were identified through the dbSNP database (NCBI), and a minimum allele frequency filter (Minor Allele Frequency – MAF) between 0.1 and 1.0 was applied for variant selection. The selected variants were submitted to the PredictSNP2.0 platform, which integrates different functional prediction algorithms and classifies alterations as neutral or deleterious. Complementary data were obtained from ClinVar, Ensembl, OMIM, RegulomeDB and UCSC Genome Browser. Results: The initial search in dbSNP identified 85,415 variants associated with the EGFR gene. After the global allele frequency filter, 943 variants were selected for further analysis, of which 306 unique variants were submitted to the PredictSNP2.0 platform. Preliminary results showed that 34 variants were classified as deleterious by more than 50% of the integrated prediction tools. Notably, the rs2072454 polymorphism, in the C/A and C/G substitutions, was considered deleterious by 100% of the algorithms evaluated. Discussion: EGFR expression has been demonstrated in a subset of AML patients, with functional activation in approximately 15% of cases, indicating a possible role for this receptor in leukemic cell biology. Although erlotinib presented limited efficacy as a single agent in relapsed/refractory AML, preclinical evidence suggests off-target activity through pathways involved in AML differentiation. The consistent classification of common EGFR polymorphisms such as rs2072454 as deleterious suggests that structural alterations may compromise receptor function and influence the interaction with tyrosine kinase inhibitors, potentially affecting therapeutic response. Conclusion: The in silico analysis identified EGFR polymorphisms with high deleteriousness scores, including rs2072454, which deserve further investigation. These variants may produce structural changes capable of impairing receptor function and modulating the response to tyrosine kinase inhibitors, representing candidates for functional validation in the context of acute myeloid leukemia.
SN - 2531-1379
SN - 2531-1387
ER -