A machine learning and deep learning-based integrated multi-omics technique for leukemia prediction

Abbasi, Erum Yousef; Deng, Zhongliang; Ali, Qasim; Khan, Adil; Shaikh, Asadullah; Reshan, Mana Saleh Al; Sulaiman, Adel; Alshahrani, Hani

doi:10.1016/j.heliyon.2024.e25369

Cited by 5 publications

(1 citation statement)

References 89 publications

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“…Moreover, incorporation of next-generation sequencing, and other high-throughput techniques have refined the discovery and validation of diagnostic and prognostic biomarkers and their incorporation into precision medicine [43][44][45][46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

Alanazi,

Siyal,

Basit

et al. 2024

Preprint

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The hallmark of Chronic Myeloid Leukemia (CML) is Philadelphia chromosome t(9:22), which leads to formation of BCR-ABL1 fusion oncogene. BCR-ABL1 induces genetic instability, causing the progression of chronic myeloid leukemia (CML) from the manageable Chronic Phase (CP-CML) to the accelerated phase (AP-CML) and ultimately to the lethal blast crisis (BC-CML). The precise mechanism responsible for CML progression are not well comprehended, and there is a lack of specific molecular biomarkers for advanced phase CML. Mutations in transcription factors (TFs) have a significant role in cancer initiation, relapses, invasion, metastasis, and resistance to anti-cancer drugs. Recently, our group reported association of a novel transcription factor, ZNF208, with CML progression and there was a dire need for clinical validation of this novel biomarker. Therefore, the aim of this study was to clinically validate mutated ZNF208 as a novel biomarker for CML progression in a larger cohort of AP- and BC-CML patients using control-case studies. A total of 73 CML patients (N=73) from King Saud University Medical City Riyadh and King Abdulaziz National Guard Hospital, Al-Ahsa, Saudi Arabia were enrolled in the study (2020-2023) , with the experimental group (cases) consisting of patients AP-CML (n=20) and BC-CML (n=12). The controls consisted of age/sex matched CP-CML (n=41). The study was approved by Research Ethics Committees of participating institutes and all patients provided informed consent for the study. Clinical evaluations for patients were conducted according to the guidelines established by the European LeukemiaNet in 2020. Targeted resequencing of ZNF 208 was employed using Illumina NextSeq500 instrument (Illumina, San Diego, CA, USA) and mutations confirmed using Sanger sequencing. Both next generation sequencing as well as Sanger sequencing identified a novel missense mutation (c.64G>A) in novel ZNF208 . in 56 (93.3) and12 (100) CP-, AP- and BC-CML patients respectively, while in none (0%) of CP-CML patients or healthy controls from genomic databases (p=0.0001). Therefore, our studies show that ZNF208 mutation (c.64G>A) is novel and very specific biomarker for AP-and BC-CML patients. ZNF208 and other such proteins may cause carcinogenesis by interacting with KAP-1 repressor to silence many target genes and thus may prove to be novel drug targets as well. Therefore, we recommend carrying out prospective clinical trials for further clinical validation of this biomarker for its utilization in clinical decision, investigating its precise role in cancer pathogenesis and investigate its potential for novel drug target in advanced phase CML patients.

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