We focus on understanding the pathogenetic mechanisms underlying leukemogenesis with a special focus on infant leukemia. In particular we are interested in unravelling the biological mechanisms that drive clonal evolution, the emergence of drug resistance, and the role of tumor heterogeneity in these processes, ultimately leading to new effective therapies. We use a combination of state-of-the-art genomic methods, including whole genome, RNA and Exome sequencing as well as single-cell DNA and RNA-sequencing and leukemia mouse models in our work.

We are currently working on the following aims

1. To identify the complement of genetic and epigenetic changes in KMT2A-R leukemia from infancy to adulthood and determine how they contribute to cellular transformation
2. To determine the clinical impact of tumor heterogeneity at single-cell resolution
3. To uncover clonal evolution in serial samples during treatment
4. To study how therapy impact clonal evolution in leukemia mouse models

Full Publication list

Selected publications

The links below will forward you to a new website.

Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia. Pilheden M, Ahlgren L, Hyrenius-Wittsten A, Gonzalez-Pena V, Sturesson H, Hansen Marquart HV, Lausen B, Castor A, Pronk CJ, Barbany G, Pokrovskaja Tamm K, Fogelstrand L, Lohi O, Norén-Nyström U, Asklin J, Chen Y, Song G, Walsh M, Ma J, Zhang J, Saal LH, Gawad C, Hagström-Andersson AK. HemaSphere. Sep 30;6(10):e785, 2022.

FLT3N676K drives acute myeloid leukemia in a xenograft model of KMT2A-MLLT3 leukemogenesis. Hyrenius-Wittsten A, Pilheden M, Falqués-Costa A, Eriksson M, Sturesson H, Schneider P, Wander P, Garcia-Ruiz C, Liu J, Ågerstam H, Hultquist A, Lilljebjörn H, Stam RW, Järås M, Hagström-Andersson AK. Leukemia. Sep;33(9):2310-2314, 2019. 

De novo activating mutations drive clonal evolution and enhances clonal fitness in KMT2A-rearranged leukemia. Hyrenius-Wittsten A, Pilheden M, Sturesson H, Hansson J, Walsh MP, Song G, Kazi J, Liu J, R Ramakrishan, C Garcia-Ruiz^, Nance S, Gupta P, Zhang J, Rönnstrand L, Hultquist A, Downing JR, Lindkvist-Petersson K, Järås M, Gruber TA, Ma J, and Hagström-Andersson AK.  Nature Communications, 2018;9,1770.

Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia. Hyrenius-Wittsten A, Sturesson H, Bidgoli M, Jonson T, Ehinger M, Lilljebjörn H, Scheding S and Andersson AK. Genes Chromosomes and Cancer 2016;55;11:847-54.

The Genomic Landscape of Core-Binding Factor Acute Myeloid Leukemias. Faber ZJ, Chen X, Larson Gedman A, Boggs K, Cheng J, Ma J, Radtke I, Chao JR, Ma J, Walsh MP, Song G, Andersson AK, Dang J, Dong L, Liu Y, Huether R, Cai Z, Mulder H, Wu G, Edmonson M, Rusch M, Qu C, Li Y, Vadodaria B, Wang J, Hedlund E, Cao X, Yergeau D, Nakitandwe J, Pounds S, Shurtleff S, Fulton R, Fulton L, Easton J, Parganas E, Pui CH, Rubnitz JE, Ding L, Mardis ER, Wilson RK, Gruber TA, Mullighan CG, Schlenk RF, Paschka P, Döhner K, Döhner H, Bullinger L, Zhang J, Klco JM, Downing JR. Nature Genetics; 2016;48:1551-1556.

Novel ETV6-RUNX1-like and DUX4-rearranged subtypes in pediatric B-cell precursor acute lymphoblastic leukemia. Lilljebjörn H, Henningsson R, Hyrenius-Wittsten A, Olsson L, Orsmark-Pietras C, von Palffy S, Askmyr M, Rissler R, Schrappe M, Cario G, Castor A, JH Pronk C, Behrendtz M, Mitelman F, Johansson B, Paulsson K, Andersson AK, Fontes M, Fioretos F.  Nature Communication 2016;7:11790.

The Genomic Landscape of Hypodiploid Acute Lymphoblastic Leukemia. Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG.  Nature Genetics 2013;45:242-5.

The landscape of somatic mutations in Infant MLL rearranged acute lymphoblastic leukemias. Andersson AK#, Ma J#, Wang J, Chen X, Larson-Gedman A, Dang J, Nakitandwe J, Holmfeldt L, Parker M, Easton J, Huether R, Kriwacki R, Rusch M, Wu G, Li Y, Mulder M,  Raimondi S, Pounds S, Guolian K, Shi L, Becksfort J, Gupta P, Payne-Turner D, Vadodaria B, Boggs K, Yergeau D, Manne J, Song G, Edmonson M, Nagawatte P, Wei L, Cheng C, Pei D, Sutton R, Venn NC, Chetcuti A, Rush A, Catchpoole D, Heldrup J, Fioretos T, C Lu, Ding L, Pui CH, Shurtleff S, Mullighan CG, Mardis ER, Wilson RK, Gruber TA, Zhang J, Downing JR for the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project. # Contributed equally. Nature Genetics, 47:330-337;2015.

IDH1 and IDH2 mutations in pediatric acute leukemia. Andersson A, Miller D, Lynch J, Lemoff A, Zhongling C, Pounds S, Radtke I, Bing Y, Schuetz J, Rubnitz J, Ribeiro R, Raimondi S, Zhang J,  Mullighan C, Shurtleff S, Schulman B, Downing J. Leukemia, 10:1570-7; 2011.

Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status. Andersson A, Ritz C, Lindgren D, Edén P, Lassen C, Heldrup J, Olofsson T, Råde J, Fontes M, Porwit-McDonald A, Behrendtz M, Höglund M, Johansson B, and Fioretos T. Leukemia, 6:1198-203;2007.

Molecular signatures in childhood acute leukemia and their correlations to expression patterns in normal hematopoietic subpopulations. Andersson A, Olofsson T, Lindgren D, Nilsson B, Ritz C, Edén P, Lassen C, Råde J, Fontes M, Mörse H, Heldrup J, Behrendtz M, Mitelman F, Höglund M, Johansson B, and Fioretos T. Proceedings of the National Academy of Sciences of the United States of America 102:19069-19074;2005. 
 

Networks in academia

We are full members of the following strategic research program:

BioCARE (Swedish Research Council Strategic Research Program)

LUCC