Epigenetic regulation of leukemia and normal blood development – Andreas Lennartsson's research group

We are identifying key mechanisms that cause epigenetic and transcriptional perturbation in AML in order to be able to find new ways to treat the disease.

microscopy image of enrichment of cells
AML is characterized by an abnormal enrichment of immature blood progenitor cells that have lost their potential to differentiate to mature blood cells. Photo: https://stock.adobe.com/se/ License to Andreas Lennartsson

The group is part of the Biosciences and Nutrition Unit.

Our research

Acute myeloid leukaemia (AML) has a poor prognosis in both, adults and children. Acute leukemia accounts for 30% of the diagnosed cases of pediatric cancer. Acute lymphoblastic leukemia (ALL) is the most common subtype in children and has good prognosis with 80-90% survival. However, pediatric and infant acute myeloid leukemia still have a poor outcome. There is therefore an urgent need for new novel therapeutics. Dramatic improvements in treatment and outcome have been made, when the biology is well-characterised. For acute promyelocytic leukaemia (APML) the long-term survival now exceeds 90%, demonstrating that a better understanding of AML biology is a pre-requisite for the development of novel therapies to improve treatment outcomes. AML is characterised by early mutations and chromosomal aberrations in epigenetic regulators and transcription factors. Therefore, we are focusing our research on epigenetic regulation and epigenetic treatment of AML in adults children and infants.

graphic illustration of tumours and genes
Disturbed epigenetic regulation in AML can lead to silencing of tumour suppressor genes and development and maintenance of AML. Illustration: by deusin https://stock.adobe.com/se/ License to Andreas Lennartsson

We are using cutting edge genome-wide technologies, biochemistry and molecular biology methods, novel model-systems and primary patient material, to obtain an increased knowledge of the molecular mechanisms that drive AML. The results are used to identify new drugs and drug combinations to develop improved treatments for AML. We are working together with several international research groups who are developing technologies to be able to analyse transcriptomics and epigenomics in new ways and in small cell populations, such as the leukemic stem cells. In addition, we have close collaborations with clinical haematologists to be able to ask the clinically important research questions. Within this network of technical know how, clinical expertise and scientific drive, we have the tools to make major advances in the treatment of AML.

Dysregulated metabolic enzymes mediate vulnerabilities for disease via epigenetic mechanisms 

The molecular interactions and crosstalk between epigenetic regulation and cellular metabolism are significantly influenced by diet and metabolism and thus are dependent on nutrient availability. Recently an intersecting mechanism has been described, suggesting that there are under-studied molecular mechanisms that facilitate epigenomic dynamics under perturbed metabolic conditions that may contribute to human disease.

Our projects include:

  • Epigenetic regulations of normal blood development, to better understand the perturbations found in AML.
  • Identifying epigenetic disturbance in AML patients.
  • Using iPS cells retrieved from AML patients as a model system to understand the molecular development of AML.
  • Testing and analysing the drug response of novel drug or drug combinations, both in vitro and by participating in clinical trials.
  • Dissect the metabolic-epigenetic molecular networks in blood cells; highlight their role in mediating cellular responses; and explore their modifiability through dietary and pharmacological interventions for metabolic associated diseases.

Work environment and values

Creating Psychological Safety in the Workplace from HBR IdeaCast.
https://podcasts.apple.com/se/podcast/hbr-ideacast/id152022135?i=1000428229584

Developed Tools and databases

EpiFactors - a tool for cell specific expression of epigenetic regulators:
https://epifactors.autosome.org/

group photo of some people standing in a snowy landscape
Group photo, Andreas Lennartsson's group, from the left: Farzaneh Varnoosfaderani Shahin, Wenbo Dong, Sophia Miliara, Anna Palau and Andreas Lennartsson.

Looking for a Postdoc or Master position?

We are always interested to recruit motivated students and postdocs!

Please contact Andreas Lennartsson for more information.

 

Publications

Selected publications

  • Article: LEUKEMIA. 2023;37(9):1830-1841
    Palau A; Segerberg F; Lidschreiber M; Lidschreiber K; Naughton AJ; Needhamsen M; Jung LA; Jagodic M; Cramer P; Lehmann S; Carlsten M; Lennartsson A
  • Article: NUCLEIC ACIDS RESEARCH. 2023;51(D1):D564-D570
    Marakulina D; Vorontsov IE; Kulakovskiy IV; Lennartsson A; Drablos F; Medvedeva YA
  • Article: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2022;23(19):11413
    Romanova EI; Zubritskiy AV; Lioznova AV; Ogunleye AJ; Golotin VA; Guts AA; Lennartsson A; Demidov ON; Medvedeva YA
  • Article: BLOOD ADVANCES. 2021;5(4):1003-1016
    Mareschal S; Palau A; Lindberg J; Ruminy P; Nilsson C; Bengtzen S; Engvall M; Eriksson A; Neddermeyer A; Marchand V; Jansson M; Bjorklund M; Jardin F; Rantalainen M; Lennartsson A; Cavelier L; Gronberg H; Lehmann S
  • Journal article: GENOME RESEARCH. 2020;30(9):1377
    Ramilowski JA; Yip CW; Agrawal S; Chang J-C; Ciani Y; Kulakovskiy IV; Mendez M; Ooi JLC; Ouyang JF; Parkinson N; Petri A; Roos L; Severin J; Yasuzawa K; Abugessaisa I; Akalin A; Antonov IV; Arner E; Bonetti A; Bono H; Borsari B; Brombacher F; Cameron CJF; Cannistraci CV; Cardenas R; Cardon M; Chang H; Dostie J; Ducoli L; Favorov A; Fort A; Garrido D; Gil N; Gimenez J; Guler R; Handoko L; Harshbarger J; Hasegawa A; Hasegawa Y; Hashimoto K; Hayatsu N; Heutink P; Hirose T; Imada EL; Itoh M; Kaczkowski B; Kanhere A; Kawabata E; Kawaji H; Kawashima T; Kelly ST; Kojima M; Kondo N; Koseki H; Kouno T; Kratz A; Kurowska-Stolarska M; Kwon ATJ; Leek J; Lennartsson A; Lizio M; Lopez-Redondo F; Luginbuhl J; Maeda S; Makeev VJ; Marchionni L; Medvedeva YA; Minoda A; Muller F; Munoz-Aguirre M; Murata M; Nishiyori H; Nitta KR; Noguchi S; Noro Y; Nurtdinov R; Okazaki Y; Orlando V; Paquette D; Parr CJC; Rackham OJL; Rizzu P; Martinez DFS; Sandelin A; Sanjana P; Semple CAM; Shibayama Y; Sivaraman DM; Suzuki T; Szumowski SC; Tagami M; Taylor MS; Terao C; Thodberg M; Thongjuea S; Tripathi V; Ulitsky I; Verardo R; Vorontsov IE; Yamamoto C; Young RS; Baillie JK; Forrest ARR; Guigo R; Hoffman MM; Hon CC; Kasukawa T; Kauppinen S; Kere J; Lenhard B; Schneider C; Suzuki H; Yagi K; de Hoon MJL; Shin JW; Carninci P
  • Article: BLOOD. 2020;136(3):339-352
    Mujahed H; Miliara S; Neddermeyer A; Bengtzen S; Nilsson C; Deneberg S; Cordeddu L; Ekwall K; Lennartsson A; Lehmann S
  • Article: EPIGENETICS. 2020;15(6-7):702-714
    Varnoosfaderani FS; Palau A; Dong W; Persson J; Durand-Dubief M; Svensson JP; Lennartsson A
  • Article: BLOOD. 2017;129(7):e13-e25
    Qu Y; Siggens L; Cordeddu L; Gaidzik VI; Karlsson K; Bullinger L; Doehner K; Ekwall K; Lehmann S; Lennartsson A
  • Article: EXPERIMENTAL HEMATOLOGY. 2015;43(8):609-624
    Eriksson A; Lennartsson A; Lehmann S
  • Article: SCIENCE. 2015;347(6225):1010-1014
    Arner E; Daub CO; Vitting-Seerup K; Andersson R; Lilje B; Drablos F; Lennartsson A; Roennerblad M; Hrydziuszko O; Vitezic M; Freeman TC; Alhendi AMN; Arner P; Axton R; Baillie JK; Beckhouse A; Bodega B; Briggs J; Brombacher F; Davis M; Detmar M; Ehrlund A; Endoh M; Eslami A; Fagiolini M; Fairbairn L; Faulkner GJ; Ferrai C; Fisher ME; Forrester L; Goldowitz D; Guler R; Ha T; Hara M; Herlyn M; Ikawa T; Kai C; Kawamoto H; Khachigian LM; Klinken SP; Kojima S; Koseki H; Klein S; Mejhert N; Miyaguchi K; Mizuno Y; Morimoto M; Morris KJ; Mummery C; Nakachi Y; Ogishima S; Okada-Hatakeyama M; Okazaki Y; Orlando V; Ovchinnikov D; Passier R; Patrikakis M; Pombo A; Qin X-Y; Roy S; Sato H; Savvi S; Saxena A; Schwegmann A; Sugiyama D; Swoboda R; Tanaka H; Tomoiu A; Winteringham LN; Wolvetang E; Yanagi-Mizuochi C; Yoneda M; Zabierowski S; Zhang P; Abugessaisa I; Bertin N; Diehl AD; Fukuda S; Furuno M; Harshbarger J; Hasegawa A; Hori F; Ishikawa-Kato S; Ishizu Y; Itoh M; Kawashima T; Kojima M; Kondo N; Lizio M; Meehan TF; Mungall CJ; Murata M; Nishiyori-Sueki H; Sahin S; Nagao-Sato S; Severin J; de Hoon MJL; Kawai J; Kasukawa T; Lassmann T; Suzuki H; Kawaji H; Summers KM; Wells C; Hume DA; Forrest ARR; Sandelin A; Carninci P; Hayashizaki Y
  • Article: EPIGENETICS & CHROMATIN. 2015;8(1):4
    Siggens L; Cordeddu L; Rnnerblad M; Lennartsson A; Ekwall K
  • Article: EPIGENETICS. 2014;9(8):1108-1119
    Qu Y; Lennartsson A; Gaidzik VI; Deneberg S; Karimi M; Bengtzen S; Hoglund M; Bullinger L; Doehner K; Lehmann S
  • Article: BLOOD. 2014;123(17):e79-e89
    Ronnerblad M; Andersson R; Olofsson T; Douagi I; Karimi M; Lehmann S; Hoof I; de Hoon M; Itoh M; Nagao-Sato S; Kawaji H; Lassmann T; Carninci P; Hayashizaki Y; Forrest ARR; Sandelin A; Ekwall K; Arner E; Lennartsson A
  • Article: BLOOD. 2014;123(17):e46-e57
    Prasad P; Ronnerblad M; Arner E; Itoh M; Kawaji H; Lassmann T; Daub CO; Forrest ARR; Lennartsson A; Ekwall K
  • Article: NATURE. 2014;507(7493):462-470
    Forrest ARR; Kawaji H; Rehli M; Baillie JK; de Hoon MJL; Haberle V; Lassmann T; Kulakovskiy IV; Lizio M; Itoh M; Andersson R; Mungall CJ; Meehan TF; Schmeier S; Bertin N; Jorgensen M; Dimont E; Arner E; Schmidl C; Schaefer U; Medvedeva YA; Plessy C; Vitezic M; Severin J; Semple CA; Ishizu Y; Young RS; Francescatto M; Alam I; Albanese D; Altschuler GM; Arakawa T; Archer JAC; Arner P; Babina M; Rennie S; Balwierz PJ; Beckhouse AG; Pradhan-Bhatt S; Blake JA; Blumenthal A; Bodega B; Bonetti A; Briggs J; Brombacher F; Burroughs AM; Califano A; Cannistraci CV; Carbajo D; Chen Y; Chierici M; Ciani Y; Clevers HC; Dalla E; Davis CA; Detmar M; Diehl AD; Dohi T; Drablos F; Edge ASB; Edinger M; Ekwall K; Endoh M; Enomoto H; Fagiolini M; Fairbairn L; Fang H; Farach-Carson MC; Faulkner GJ; Favorov AV; Fisher ME; Frith MC; Fujita R; Fukuda S; Furlanello C; Furuno M; Furusawa J-I; Geijtenbeek TB; Gibson AP; Gingeras T; Goldowitz D; Gough J; Guhl S; Guler R; Gustincich S; Ha TJ; Hamaguchi M; Hara M; Harbers M; Harshbarger J; Hasegawa A; Hasegawa Y; Hashimoto T; Herlyn M; Hitchens KJ; Sui SJH; Hofmann OM; Hoof I; Hori F; Huminiecki L; Iida K; Ikawa T; Jankovic BR; Jia H; Joshi A; Jurman G; Kaczkowski B; Kai C; Kaida K; Kaiho A; Kajiyama K; Kanamori-Katayama M; Kasianov A; Kasukawa T; Katayama S; Kato S; Kawaguchi S; Kawamoto H; Kawamura YI; Kawashima T; Kempfle JS; Kenna TJ; Kere J; Khachigian LM; Kitamura T; Klinken SP; Knox AJ; Kojima M; Kojima S; Kondo N; Koseki H; Koyasu S; Krampitz S; Kubosaki A; Kwon AT; Laros JFJ; Lee W; Lennartsson A; Li K; Lilje B; Lipovich L; Mackay-sim A; Manabe R-I; Mar JC; Marchand B; Mathelier A; Mejhert N; Meynert A; Mizuno Y; Morais DADL; Morikawa H; Morimoto M; Moro K; Motakis E; Motohashi H; Mummery CL; Murata M; Nagao-Sato S; Nakachi Y; Nakahara F; Nakamura T; Nakamura Y; Nakazato K; Van Nimwegen E; Ninomiya N; Nishiyori H; Noma S; Nozaki T; Ogishima S; Ohkura N; Ohmiya H; Ohno H; Ohshima M; Okada-Hatakeyama M; Okazaki Y; Orlando V; Ovchinnikov DA; Pain A; Passier R; Patrikakis M; Persson H; Piazza S; Prendergast JGD; Rackham OJL; Ramilowski JA; Rashid M; Ravasi T; Rizzu P; Roncador M; Roy S; Rye MB; Saijyo E; Sajantila A; Saka A; Sakaguchi S; Sakai M; Sato H; Satoh H; Savvi S; Saxena A; Schneider C; Schultes EA; Schulze-Tanzil GG; Schwegmann A; Sengstag T; Sheng G; Shimoji H; Shimoni Y; Shin JW; Simon C; Sugiyama D; Sugiyama T; Suzuki M; Suzuki N; Swoboda RK; 't Hoen PAC; Tagami M; Takahashi N; Takai J; Tanaka H; Tatsukawa H; Tatum Z; Thompson M; Toyoda H; Toyoda T; Valen E; van de Wetering M; van den Berg LM; Verardo R; Vijayan D; Vorontsov IE; Wasserman WW; Watanabe S; Wells CA; Winteringham LN; Wolvetang E; Wood EJ; Yamaguchi Y; Yamamoto M; Yoneda M; Yonekura Y; Yoshida S; Zabierowski SE; Zhang PG; Zhao X; Zucchelli S; Summers KM; Suzuki H; Daub CO; Kawai J; Heutink P; Hide W; Freeman TC; Lenhard B; Bajic VB; Taylor MS; Makeev VJ; Sandelin A; Hume DA; Carninci P; Hayashizaki Y
  • Article: NATURE. 2014;507(7493):455-461
    Andersson R; Gebhard C; Miguel-Escalada I; Hoof I; Bornholdt J; Boyd M; Chen Y; Zhao X; Schmidl C; Suzuki T; Ntini E; Arner E; Valen E; Li K; Schwarzfischer L; Glatz D; Raithel J; Lilje B; Rapin N; Bagger FO; Jorgensen M; Andersen PR; Bertin N; Rackham O; Burroughs AM; Baillie JK; Ishizu Y; Shimizu Y; Furuhata E; Maeda S; Negishi Y; Mungall CJ; Meehan TF; Lassmann T; Itoh M; Kawaji H; Kondo N; Kawai J; Lennartsson A; Daub CO; Heutink P; Hume DA; Jensen TH; Suzuki H; Hayashizaki Y; Mueller F; Forrest ARR; Carninci P; Rehli M; Sandelin A

Staff and contact

Group leader

All members of the group

Keywords:
Cell and Molecular Biology Hematology Medical Biotechnology (focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
AL
Content reviewer:
03-09-2024