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BRIEF RESEARCH REPORT article

Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1442539
This article is part of the Research Topic Screening and discovering novel biological biomarkers by omic-data to revolutionize tumor management View all 3 articles

Multi-omic analysis of longitudinal acute myeloid leukemia patient samples reveals the potential prognostic markers linked to disease progression

Provisionally accepted
Nisar Ahmed Nisar Ahmed 1Irene Cavattoni Irene Cavattoni 2William Villiers William Villiers 1,3Chiara Cugno Chiara Cugno 4Sara Deola Sara Deola 4Borbala Mifsud Borbala Mifsud 1*
  • 1 Hamad bin Khalifa University, Doha, Qatar
  • 2 Ospedale di Bolzano, Bolzano, Italy
  • 3 Department of Medical and Molecular Genetics, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, England, United Kingdom
  • 4 Advanced Cell Therapy Core, Research, Sidra Medicine, Doha, Qatar, Doha, Qatar

The final, formatted version of the article will be published soon.

    Relapse remains a determinant of treatment failure and contributes significantly to mortality in acute myeloid leukemia (AML) patients. Despite efforts to understand AML progression and relapse mechanisms, findings on acquired gene mutations in relapse vary, suggesting inherent genetic heterogeneity and emphasizing the role of epigenetic modifications. We conducted a multi-omic analysis using Omni-C, ATAC-seq, and RNA-seq on longitudinal samples from two adult AML patients at diagnosis and relapse. Herein, we characterized genetic and epigenetic changes in AML progression to elucidate the underlying mechanisms of relapse. Differential interaction analysis showed significant 3D chromatin landscape reorganization between relapse and diagnosis samples. Comparing global open chromatin profiles revealed that relapse samples had significantly fewer accessible chromatin regions than diagnosis samples. In addition, we discovered that relapse-related upregulation was achieved either by forming new active enhancer contacts or by losing interactions with poised enhancers/potential silencers. Altogether, our study highlights the impact of genetic and epigenetic changes on AML progression, underlining the importance of multi-omic approaches in understanding disease relapse mechanisms and guiding potential therapeutic interventions.

    Keywords: AML Relapse, Multi-omic analyses, Chromatin reorganization, epigenetic modifications, Omni-C, ATAC-seq, RNA-Seq

    Received: 02 Jun 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Ahmed, Cavattoni, Villiers, Cugno, Deola and Mifsud. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Borbala Mifsud, Hamad bin Khalifa University, Doha, Qatar

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