Epigenetic regulation of leukemia and normal blood development - Andreas Lennartsson

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

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.

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.

Group members

Anna Palau De Miguel

Postdoctoral researcher

Xiangfu Zhong

Postdoctoral researcher
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.

 

Selected publications

Challenging conventional karyotyping by next-generation karyotyping in 281 intensively treated patients with AML.
Mareschal S, Palau A, Lindberg J, Ruminy P, Nilsson C, Bengtzén S, Engvall M, Eriksson A, Neddermeyer A, Marchand V, Jansson M, Björklund M, Jardin F, Rantalainen M, Lennartsson A, Cavelier L, Grönberg H, Lehmann S
Blood Adv 2021 02;5(4):1003-1016

Functional annotation of human long noncoding RNAs via molecular phenotyping.
Ramilowski JA, Yip CW, Agrawal S, Chang JC, et al
Genome Res 2020 07;30(7):1060-1072

AML displays increased CTCF occupancy associated with aberrant gene expression and transcription factor binding.
Mujahed H, Miliara S, Neddermeyer A, Bengtzén S, Nilsson C, Deneberg S, Cordeddu L, Ekwall K, Lennartsson A, Lehmann S
Blood 2020 07;136(3):339-352

A regulatory role for CHD2 in myelopoiesis.
Shahin Varnoosfaderani F, Palau A, Dong W, Persson J, Durand-Dubief M, Svensson JP, Lennartsson A
Epigenetics ;15(6-7):702-714

Depletion of the transcriptional coactivators CREB-binding protein or EP300 downregulates CD20 in diffuse large B-cell lymphoma cells and impairs the cytotoxic effects of anti-CD20 antibodies.
Scialdone A, Khazaei S, Hasni MS, Lennartsson A, Gullberg U, Drott K
Exp Hematol 2019 11;79:35-46.e1

Cancer-specific changes in DNA methylation reveal aberrant silencing and activation of enhancers in leukemia.
Qu Y, Siggens L, Cordeddu L, Gaidzik VI, Karlsson K, Bullinger L, Döhner K, Ekwall K, Lehmann S, Lennartsson A
Blood 2017 02;129(7):e13-e25

Epigenetic aberrations in acute myeloid leukemia: Early key events during leukemogenesis.
Eriksson A, Lennartsson A, Lehmann S
Exp Hematol 2015 Aug;43(8):609-24

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.
Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drabløs F, Lennartsson A, et al
Science 2015 Feb;347(6225):1010-4

Transcription-coupled recruitment of human CHD1 and CHD2 influences chromatin accessibility and histone H3 and H3.3 occupancy at active chromatin regions.
Siggens L, Cordeddu L, Rönnerblad M, Lennartsson A, Ekwall K
Epigenetics Chromatin 2015 ;8(1):4

Differential methylation in CN-AML preferentially targets non-CGI regions and is dictated by DNMT3A mutational status and associated with predominant hypomethylation of HOX genes.
Qu Y, Lennartsson A, Gaidzik VI, Deneberg S, Karimi M, Bengtzén S, Höglund M, Bullinger L, Döhner K, Lehmann S
Epigenetics 2014 Aug;9(8):1108-19

Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation.
Rönnerblad 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 AR, Sandelin A, Ekwall K, Arner E, Lennartsson A,
Blood 2014 Apr;123(17):e79-89

High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis.
Prasad P, Rönnerblad M, Arner E, Itoh M, Kawaji H, Lassmann T, Daub CO, Forrest AR, Lennartsson A, Ekwall K,
Blood 2014 Apr;123(17):e46-57

A promoter-level mammalian expression atlas.
FANTOM Consortium and the RIKEN PMI and CLST (DGT), Forrest AR, Kawaji H, Rehli M, et al
Nature 2014 Mar;507(7493):462-70

An atlas of active enhancers across human cell types and tissues.
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, Jørgensen 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, Müller F, Forrest ARR, Carninci P, Rehli M, Sandelin A
Nature 2014 Mar;507(7493):455-461