Department of Medical Sciences

Epigenetics and genomics of acute leukemia

In our research project on pediatric acute lymphoblastic leukemia (ALL) we are using genome-wide genotyping and “next generation” DNA sequencing for analysis of DNA methylation, fusion genes and genomic sequence variation in DNA and RNA samples from patients with ALL. The aim of the project is to identify genetic and epigenetic signatures that may be used as biomarkers for prognosis of the disease progression and response to treatment in individual patients. We are involved in similar research also in pediatric acute myeloid leukemia (AML). A second objective of our project is to gain in-sights into mechanisms by which DNA methylation transforms normal hematopoetic cells into leukemic cells, and affects treatment responses in acute leukemia.

In the project we are analyzing unique collection of bone marrow and blood samples from children with acute leukemia, collected in the Nordic countries by the Nordic Society for Paediatric Oncology (NOPHO). The project involves a close collaboration with pediatric oncologists at the Academic Childrens’ Hospital in Uppsala.

Group members working in the project

  • Johan Dahlberg
  • Anders Lundmark
  • Yanara Marincevic
  • Jessica Nordlund

Former group members active in the project

  • Eva Berglund
  • Mårten Lindqvist

Main collaborators

Prof. Gudmar Lönnerholm, and Dr Josefine Palle, Department of Women's and Children's Health, Uppsala University Children's Hospital.

Funding

Swedish Cancer Society
Foundation for Paediatric Cancer Research
Swedish Research Council for Science & Technology (VR-NT)

Recent publications

  • Marincevic-Zuniga Y, Dahlberg J, Nilsson S, Raine A, Nystedt S, Lindqvist CM, Berglund EC, Abrahamsson J, Cavelier L, Forestier E, Heyman M, Lönnerholm G, Nordlund J, Syvänen AC (2017) Transcriptome sequencing in pediatric acute lymphoblastic leukemia identifies fusion genes associated with distinct DNA methylation profiles. J Hematol Oncol 10(1), 148
  • Teppo S, Laukkanen S, Liuksiala T, Nordlund J, Oittinen M, Teittinen KJ, Grönroos T, St-Onge P, Sinnett D, Syvänen A-C, Nykter M, Viiri K, Heinäniemi M, Lohi O (2016) Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia. Genome Res 26(11), 1468-1477
  • Wahlberg P, Lundmark A, Nordlund J, Busche S, Raine A, Tandre K, Rönnblom L, Sinnett D, Forestier E, Pastinen T, Lönnerholm G, Syvänen A-C (2016) DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands. Epigenomics 8(10), 1367-1387
  • Lindqvist CM, Lundmark A, Nordlund J, Freyhult E, Ekman D, Carlsson Almlöf J, Raine A, Övernäs E, Abrahamsson J, Frost B-M, Grandér D, Heyman M, Palle J, Forestier E, Lönnerholm G, Berglund EC, Syvänen A-C (2016) Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes. Oncotarget 7(39), 64071-64088
  • Marzouka N-a-d, Nordlund J, Bäcklin CL, Lönnerholm G, Syvänen A-C, Almlöf JC (2016) CopyNumber450kCancer: Baseline Correction for Accurate Copy Number Calling from the 450k Methylation Array. Bioinformatics 32(7), 1080-1082
  • Marincevic-Zuniga Y, Zachariadis V, Cavelier L, Castor A, Barbany G, Forestier E, Fogelstrand L, Heyman M, Abrahamsson J, Lönnerholm G, Nordgren A, Syvänen A-C, Nordlund J (2016) PAX5-ESRRB is a recurrent fusion gene in B-cell precursor pediatric acute lymphoblastic leukemia. Haematologica 101(1), e20-e23
  • Lindqvist CM, Nordlund J, Ekman D, Johansson A, Moghadam BT, Raine A, Övernäs E, Dahlberg J, Wahlberg P, Henriksson N, Abrahamsson J, Frost B-M, Grandér D, Heyman M, Larsson R, Palle J, Söderhäll S, Forestier E, Lönnerholm G, Syvänen A-C, Berglund EC (2015) The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing. Hum Mutat 36(1), 118-128
  • Nordlund J, Backlin C, Zachariadis V, Cavelier L, Dahlberg J, Ofverholm I, Barbany G, Nordgren A, Overnas E, Abrahamsson J, Flaegstad T, Heyman M, Jonsson O, Kanerva J, Larsson R, Palle J, Schmiegelow K, Gustafsson M, Lonnerholm G, Forestier E, Syvanen A-C (2015) DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia. Clin Epigenetics 7(1), 11