بيانات النشر: Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten)
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Department of Pediatrics and Adolescent Medicine, Aarhus University, Aarhus, Denmark
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Children’s Hospital, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
Norwegian Institute of Public Health, Oslo, Norway; Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Washington National Primate Research Center, Seattle, USA
Department of Immunology, Genetics and Pathology; The Beijer Laboratory, Uppsala, Sweden
American Society of Hematology
نبذة مختصرة : 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.
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