Open this publication in new window or tab >>Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Uppsala University, Science for Life Laboratory, SciLifeLab. National Bioinformatics Infrastructure Sweden.
Department of Molecular Biology, National Bioinformatics Infrastructure Sweden; Science for Life Laboratory, Umeå University, Sweden.
Department of Clinical Medicine, Department of Pediatrics and Adolescent Medicine, Aarhus University, Denmark.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatric oncological and neurological research.
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, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics. Uppsala University, Swedish Collegium for Advanced Study (SCAS). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. The Institute of Computer Science, Polish Academy of Sciences, Warsaw, Poland; Washington National Primate Research Center, Seattle, WA, USA; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Umeå University, Umeå, Sweden; Department of Clinical Medicine and Department of Pediatrics and Adolescent Medicine, Aarhus University, Aarhus, Denmark; Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Norwegian Institute of Public Health, Oslo, Norway; Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Department of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2022 (English)In: Blood Advances, ISSN 2473-9529 , E-ISSN 2473-9537, Vol. 6, no 1, p. 152-164Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
American Society of HematologyAmerican Society of Hematology (ASH), 2022
Keywords
Acute myeloid leukemia, RNA-sequencing, relapse and resistance, machine learning-based analysis
National Category
Cancer and Oncology Hematology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-427202 (URN)10.1182/bloodadvances.2021004962 (DOI)000753720500016 ()34619772 (PubMedID)
Funder
Swedish Research Council, 2018-05973Knut and Alice Wallenberg Foundation, 2013-0159Swedish National Infrastructure for Computing (SNIC), sens2017604Swedish National Infrastructure for Computing (SNIC), sens2018512Swedish Research Council, 2013-03486Swedish Childhood Cancer Foundation, PR2013-0070Swedish Childhood Cancer Foundation, TJ2013-0045Swedish Cancer Society, CAN2013/489Kjell and Marta Beijer FoundationeSSENCE - An eScience CollaborationNIH (National Institute of Health), HHSN272201700010I
Note
De två första författarna delar förstaförfattarskapet
2020-12-032020-12-032024-01-15Bibliographically approved