Transcriptomic analysis reveals proinflammatory signatures associated with acute myeloid leukemia progression
Year: 2021
Type: article
Study design: Observational Study
Abstract: Numerous studies have been performed over the last decade to exploit the complexity of genomic and transcriptomic lesions driving the initiation of acute myeloid leukemia (AML). These studies have helped improve risk classification and treatment options. Detailed molecular characterization of longitudinal AML samples is sparse, however; meanwhile, relapse and therapy resistance represent the main challenges in AML care. To this end, we performed transcriptome-wide RNA sequencing of longitudinal diagnosis, relapse, and/or primary resistant samples from 47 adult and 23 pediatric AML patients with known mutational background. Gene expression analysis revealed the association of short event-free survival with overexpression of GLI2 and IL1R1, as well as downregulation of ST18. Moreover, CR1 downregulation and DPEP1 upregulation were associated with AML relapse both in adults and children. Finally, machine learning-based and network-based analysis identified overexpressed CD6 and downregulated INSR as highly copredictive genes depicting important relapse-associated characteristics among adult patients with AML. Our findings highlight the importance of a tumor-promoting inflammatory environment in leukemia progression, as indicated by several of the herein identified differentially expressed genes. Together, this knowledge provides the foundation for novel personalized drug targets and has the potential to maximize the benefit of current treatments to improve cure rates in AML.
Source: Blood Advances
Authors: Svea Stratmann, Sara A. Yones, Mateusz Garbulowski, Jitong Sun, Aron Skaftason, Markus Mayrhofer, Nina Norgren, Morten Krogh Herlin, Christer Sundström, Anna Eriksson, Martin Höglund, Josefine Palle, Jonas Abrahamsson, Kirsi Jahnukainen, Monica Cheng Munthe-Kaas, Bernward Zeller, Katja Pokrovskaja Tamm, Lucia Cavelier, Jan Komorowski, Linda Holmfeldt
Institutions: Uppsala University, Science for Life Laboratory, Karolinska Institutet, National Bioinformatics Infrastructure Sweden, Umeå University, Aarhus University, Department of Medical Sciences, Department of Medical Sciences, University of Gothenburg, University of Helsinki, Helsinki University Hospital, Oslo University Hospital, Norwegian Institute of Public Health, Karolinska University Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,892
Funders: University of Washington, European Hematology Association, Cancerfonden, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Akademiska Sjukhuset, Barncancerfonden, Uppsala Universitet, Science for Life Laboratory, National Institutes of Health, Uppsala Multidisciplinary Center for Advanced Computational Science, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W3126346508