Abstract 4638: Investigations on association of prognostically important pan-cancer genes with disease progression and acute transformation in CML indicate involvement of diverse cellular mechanisms
Authors: Sabreen Alanazi, Sarah Alfayez, Maryam Butuwaybah, Nawaf Alanazi, Abdulkareem Algarni, Kanza Adeel, Yaqob Taleb, Aamir Aleem, Aemir Mohammed, Zafar Iqbal
Journal: Cancer Research (2025)

Abstract Chronic myeloid leukemia (CML) is caused by the abnormal fusion of the bcr-abl gene which leads to the overexpression of tyrosine kinase function. Tyrosine kinase inhibitors (TKI) are targetable drugs that inhibit the kinase activity of the bcr-abl oncoprotein. They have been used over the last two decades and have shown tremendous efficacy in treating CML, specifically in chronic phase (CP-CML) and accelerated phase CML patients (AP-CML). However, disease progression to advanced stages, specifically blast crisis CML (BC-CML), leads to TKI resistance, morbidities and subsequently death, with a median overall survival of less than 2 years, despite all innovations in diagnosis, risk stratification and treatment modalities. Therefore, further investigations of gene mutations associated with CML progression is primarily essential in accurate prognostic stratification and patient-tailored treatment of advanced phase CML. As cancer is a molecular disease, different types of cancers have recently reported to share many common genomic variants. Therefore, this study aimed to investigate the association of prognostically-important pan-cancer genes with advanced phases in CML patients. The study included a total of 73 CML patients at different CML Phases (CP=41, AP=20, BC=12). The study was approved by Institutional Review Board of the participating centers and was carried out per regulations of the Declaration of Helsinki. Whole exome sequencing (WES) was conducted using Illumina NextSeq500 platform using compatible kits per manufacturer’s instructions. Healthy controls were included from genomic databases. All study subjects were screened for prognostically important pan-cancer gene mutations. Genes exclusively and commonly shared with each CML phase were subjected to further analyses. The data was analyzed using SSPS Ver. 26. The first data a total of 64 genes with 2531 mutations were detected in BC-CML patients that were absent in chronic phase CML (CP-CML) as well as healthy controls, indicating that these genes/mutations are exclusively associated with BC-CML. RPTOR was the most common gene mutated (7.35%) and chromosome 17 was the most encountered (16.32%) while chromosome 12 was the least involved (0.04%). The second data 55 genes in the accelerated phase while 83 genes in BC. Therefore, we conclude that many gene mutations associated with BC-CML are associated with different types of leukemias and solid tumors. Moreover, these genes were found to have resistance causing mutations with various underlying. Mechanisms in cell signaling, which could potentially impact treatment and prognosis of advanced phases CML patients. Citation Format: Sabreen Alanazi, Sarah Alfayez, Maryam Butuwaybah, Nawaf Alanazi, Abdulkareem Algarni, Kanza Adeel, Yaqob Taleb, Aamir Aleem, Aemir Mohammed, Zafar Iqbal. Investigations on association of prognostically important pan-cancer genes with disease progression and acute transformation in CML indicate involvement of diverse cellular mechanisms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4638.