-Omics of acute leukemia
We use modern technology for analysis of DNA, RNA, and protein levels in bulk and single-cells from patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The aim of our research is to identify genetic, epigenetic or protein signatures that can be used as biomarkers and may render new knowledge on cellular mechanisms behind treatment response, cancer dissemination, toxicity and outcome. A second objective of our project is machine and deep learning implementation to uncover hidden patterns on patient -omics data aiming to improve diagnosis and subtype classification on the individual level, which may lead to new options for precision treatment and improved long-term survival in the future.
In our projects we are analyzing samples from a 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 projects involve a close collaboration with pediatric oncologists at the Children’s Hospital in Uppsala.
Group members working in the project
- Jessica Nordlund
- Ann-Christine Syvänen
- Anna Pia Enblad
- Olga Krali
- Mariya Lysenkova
- Gustav Arvidsson
- Anders Lundmark
Former group members active in the project
- Yanara Marincevic-Zuniga
- Alva Anette
Main collaborators
- Prof. Arja Harila-Saari, Dr Josefine Palle & Prof Emeritus Gudmar Lönnerholm, Department of Women's and Children's Health, Uppsala University Children's Hospital: https://kbh.uu.se/forskning/barnonkologisk-och-neurologisk-forskning
Funding
- Swedish Research Council
- Foundation for Paediatric Cancer Research
- The Göran Gustafsson Foundation
- The Swedish Cancer Society
Selected Recent Publications
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Krali O, Palle J, Bäcklin C, Abrahamsson J, Norén-Nyström U, Hasle H, Jahnukainen K, Gísli Jónsson Ó, Hovland R, Lausen B, Larsson R, Palmqvist L, Staffas A, Zeller B, Nordlund J (2021) DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML). Genes 12(6)
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Sayyab S, Lundmark A, Larsson M, Ringnér M, Nystedt S, Marincevic-Zuniga Y, Pokrovskaja-Tamm K, Abrahamsson J, Fogelstrand L, Heyman M, Norén-Nyström U, Lönnerholm G, Harila-Saari A, Berglund EC, Nordlund J, Syvänen AC (2021) Mutational patterns and clonal evolution from diagnosis to relapse in pediatric acute lymphoblastic leukemia. Sci Rep 11,
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Chen D, Camponeschi A, Nordlund J, Marincevic‐Zuniga Y, Abrahamsson J, Lönnerholm G, Fogelstrand L, Mårtensson IL (2021) RAG1 co‐expression signature identifies ETV6‐RUNX1‐like B‐cell precursor acute lymphoblastic leukemia in children. Cancer Medicine
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Duran-Ferrer M, Clot G, Nadeu F, Beekman R, Baumann T, Nordlund J, Marincevic-Zuniga Y, … Campo E, Martin-Subero JI (2020) The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome Nat Cancer 1
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Watanabe A, Miyake K, Nordlund J, Syvänen AC, ... Inukai T (2020) Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL. Blood 136 (20)
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Nordlund J, Marincevic-Zuniga Y, Cavelier L, Raine A, Martin T, Lundmark A, Abrahamsson J, Norén-Nyström U, Lönnerholm G, Syvänen AC (2020) Refined detection and phasing of structural aberrations in pediatric acute lymphoblastic leukemia by linked-read whole-genome sequencing. Sci Rep 10
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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
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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
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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
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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
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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
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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