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Sökning: WFRF:(Höglund K.) > (2020-2023) > Genomic characteriz...

Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets

Stratmann, Svea, 1989- (författare)
Uppsala universitet,Experimentell och klinisk onkologi,Linda Holmfeldt,Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Yones, Sara A. (författare)
Gothenburg University,Göteborgs universitet,Uppsala universitet,Karolinska Institutet,Institutionen för cell- och molekylärbiologi,Science for Life Laboratory, SciLifeLab,Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
Mayrhofer, Markus, 1981- (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Norgren, Nina (författare)
Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)
Skaftason, A. (författare)
Department of Molecular Medicine and Surgery; Karolinska Institutet, Stockholm, Sweden
Sun, Jitong (författare)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Smolinska, Karolina (författare)
Uppsala universitet,Beräkningsbiologi och bioinformatik,Science for Life Laboratory, SciLifeLab,Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden
Komorowski, Jan (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Beräkningsbiologi och bioinformatik,Kollegiet för avancerade studier (SCAS),The Institute of Computer Science, Polish Academy of Sciences, Warsaw, Poland; Washington National Primate Research Center, Seattle, WA, USA,Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden; Swedish Collegium for Advanced Study, Uppsala, Sweden; Institute of Computer Science, Polish Academy of Sciences, Warsaw, Poland; Washington National Primate Research Center, WA, Seattle, United States
Herlin, M. K. (författare)
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Pediatrics and Adolescent Medicine, Aarhus University, Aarhus, Denmark
Sundström, Christer (författare)
Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Eriksson, Anna, 1977- (författare)
Uppsala universitet,Hematologi,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Höglund, Martin (författare)
Uppsala universitet,Hematologi,Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Palle, Josefine, 1964- (författare)
Uppsala universitet,Barnneurologi/Barnonkologi,Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
Abrahamsson, Jonas, 1954 (författare)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
Jahnukainen, K. (författare)
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland,Children's Hospital, University of Helsinki, Helsinki, Finland; Helsinki University Central Hospital, Helsinki, Finland
Munthe-Kaas, M. C. (författare)
Norwegian Institute of Public Health, Oslo, Norway; Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
Zeller, B. (författare)
Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
Tamm, K. P. (författare)
Karolinska Institutet,Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden
Cavelier, Lucia (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik,Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Holmfeldt, Linda (författare)
Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,The Beijer Laboratory, Uppsala, Sweden,Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Beijer Laboratory, Uppsala, Sweden
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 (creator_code:org_t)
2021-02-09
2021
Engelska.
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:3, s. 900-912
Relaterad länk:
https://ashpublicati...
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https://gup.ub.gu.se...
https://doi.org/10.1...
http://kipublication...
https://urn.kb.se/re...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Relapse is the leading cause of death of adult and pediatric patients with acute myeloid leukemia (AML). Numerous studies have helped to elucidate the complex mutational landscape at diagnosis of AML, leading to improved risk stratification and new therapeutic options. However, multi-whole-genome studies of adult and pediatric AML at relapse are necessary for further advances. To this end, we performed whole-genome and whole-exome sequencing analyses of longitudinal diagnosis, relapse, and/or primary resistant specimens from 48 adult and 25 pediatric patients with AML. We identified mutations recurrently gained at relapse in ARID1A and CSF1R, both of which represent potentially actionable therapeutic alternatives. Further, we report specific differences in the mutational spectrum between adult vs pediatric relapsed AML, with MGA and H3F3A p.Lys28Met mutations recurrently found at relapse in adults, whereas internal tandem duplications in UBTF were identified solely in children. Finally, our study revealed recurrent mutations in IKZF1, KANSL1, and NIPBL at relapse. All of the mentioned genes have either never been reported at diagnosis in de novo AML or have been reported at low frequency, suggesting important roles for these alterations predominantly in disease progression and/or resistance to therapy. Our findings shed further light on the complexity of relapsed AML and identified previously unappreciated alterations that may lead to improved outcomes through personalized medicine.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Pediatrik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Pediatrics (hsv//eng)

Nyckelord

somatic mutations
clonal evolution
landscape
diagnosis
transplant
management
patterns
complex
Hematology
acute myeloid leukemia
Medical Genetics

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

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