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Sökning: onr:"swepub:oai:DiVA.org:uu-526565" > Refining risk predi...

Refining risk prediction in pediatric acute lymphoblastic leukemia through DNA methylation profiling

Orgueira, Adrian Mosquera (författare)
Univ Hosp Santiago De Compostela, Dept Hematol, Compostela, Spain.;Hlth Res Inst Santiago De Compostela, Compostela, Spain.,Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain; Health Research Institute of Santiago de Compostela, Compostela, Spain
Krali, Olga (författare)
Uppsala universitet,Molekylär precisionsmedicin,Science for Life Laboratory, SciLifeLab,Department of Medical Sciences, Molecular Precision Medicine, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Miguez, Carlos Perez (författare)
Hlth Res Inst Santiago De Compostela, Compostela, Spain.,Health Research Institute of Santiago de Compostela, Compostela, Spain
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Raindo, Andres Peleteiro (författare)
Univ Hosp Santiago De Compostela, Dept Hematol, Compostela, Spain.;Hlth Res Inst Santiago De Compostela, Compostela, Spain.,Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain; Health Research Institute of Santiago de Compostela, Compostela, Spain
Arias, Jose Angel Diaz (författare)
Univ Hosp Santiago De Compostela, Dept Hematol, Compostela, Spain.;Hlth Res Inst Santiago De Compostela, Compostela, Spain.,Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain; Health Research Institute of Santiago de Compostela, Compostela, Spain
Perez, Marta Sonia Gonzalez (författare)
Univ Hosp Santiago De Compostela, Dept Hematol, Compostela, Spain.;Hlth Res Inst Santiago De Compostela, Compostela, Spain.,Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain; Health Research Institute of Santiago de Compostela, Compostela, Spain
Encinas, Manuel Mateo Perez (författare)
Univ Hosp Santiago De Compostela, Dept Hematol, Compostela, Spain.;Hlth Res Inst Santiago De Compostela, Compostela, Spain.,Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain; Health Research Institute of Santiago de Compostela, Compostela, Spain
Sanmartin, Manuel Fernandez (författare)
Hlth Res Inst Santiago De Compostela, Compostela, Spain.;Univ Hosp Santiago De Compostela, Dept Pediat Med, Santiago De Compostela, Spain.,Health Research Institute of Santiago de Compostela, Compostela, Spain; Department of Pediatric Medicine, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Sinnet, Daniel (författare)
CHU St Justine, Res Ctr, Montreal, PQ, Canada.;Univ Montreal, Dept Pediat, Montreal, PQ, Canada.,Research Center, CHU Sainte-Justine, Montréal, Canada; Department of Pediatrics, Université de Montréal, Montreal, Canada
Heyman, Mats (författare)
Karolinska Inst, Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Childhood Canc Res Unit, Stockholm, Sweden.;Nord Soc Pediat Hematol & Oncol NOPHO, Stockholm, Sweden.,Childhood Cancer Research Unit, Karolinska Institutet, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden; For the Nordic Society of Pediatric Hematology and Oncology (NOPHO), Stockholm, Sweden
Lönnerholm, Gudmar, 1941- (författare)
Uppsala universitet,Barnonkologisk och neurologisk forskning,Nord Soc Pediat Hematol & Oncol NOPHO, Stockholm, Sweden.,Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; For the Nordic Society of Pediatric Hematology and Oncology (NOPHO), Stockholm, Sweden
Norén-Nyström, Ulrika (författare)
Umeå universitet,Pediatrik,For the Nordic Society of Pediatric Hematology and Oncology (NOPHO), Stockholm, Sweden,Umeå Univ, Dept Clin Sci, Pediat, Umeå, Sweden.;Nord Soc Pediat Hematol & Oncol NOPHO, Stockholm, Sweden.
Schmiegelow, Kjeld (författare)
Rigshosp, Pediat & Adolescent Med, Copenhagen, Denmark.;Univ Copenhagen, Inst Clin Med, Med Fac, Copenhagen, Denmark.;Nord Soc Pediat Hematol & Oncol NOPHO, Stockholm, Sweden.,Pediatrics and Adolescent Medicine, Rigshospitalet, and the Medical Faculty, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; For the Nordic Society of Pediatric Hematology and Oncology (NOPHO), Stockholm, Sweden
Nordlund, Jessica (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär precisionsmedicin,Department of Medical Sciences, Molecular Precision Medicine, Uppsala University, Uppsala, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Univ Hosp Santiago De Compostela, Dept Hematol, Compostela, Spain;Hlth Res Inst Santiago De Compostela, Compostela, Spain. Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain; Health Research Institute of Santiago de Compostela, Compostela, Spain (creator_code:org_t)
BioMed Central (BMC), 2024
2024
Engelska.
Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 16:1
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children, and despite considerable progress in treatment outcomes, relapses still pose significant risks of mortality and long-term complications. To address this challenge, we employed a supervised machine learning technique, specifically random survival forests, to predict the risk of relapse and mortality using array-based DNA methylation data from a cohort of 763 pediatric ALL patients treated in Nordic countries. The relapse risk predictor (RRP) was constructed based on 16 CpG sites, demonstrating c-indexes of 0.667 and 0.677 in the training and test sets, respectively. The mortality risk predictor (MRP), comprising 53 CpG sites, exhibited c-indexes of 0.751 and 0.754 in the training and test sets, respectively. To validate the prognostic value of the predictors, we further analyzed two independent cohorts of Canadian (n = 42) and Nordic (n = 384) ALL patients. The external validation confirmed our findings, with the RRP achieving a c-index of 0.667 in the Canadian cohort, and the RRP and MRP achieving c-indexes of 0.529 and 0.621, respectively, in an independent Nordic cohort. The precision of the RRP and MRP models improved when incorporating traditional risk group data, underscoring the potential for synergistic integration of clinical prognostic factors. The MRP model also enabled the definition of a risk group with high rates of relapse and mortality. Our results demonstrate the potential of DNA methylation as a prognostic factor and a tool to refine risk stratification in pediatric ALL. This may lead to personalized treatment strategies based on epigenetic profiling.

Ämnesord

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)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

Nyckelord

Pediatric acute lymphoblastic leukemia
Epigenetics
DNA methylation
Machine learning
Artificial intelligence
Relapse risk
Mortality risk
Precision medicine

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