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Andreas Lennartsson has a master in Biotechnology from Lund University in Sweden. He did his PhD in Experimental hematology also at Lund University. After his PhD he contunied to the OMICS center at RIKEN in JAPAN for post-doc training in Piero Carninci's group. He carried out his second post-doc i Karl Ekwall's group at Karolinska Institute, where he is now leading a sub-group in Prof. Ekwall's laboratory.

Research description

Epigenetic regulation of myelopoiesis and its role in acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common form of acute leukemia. It is characterised by high mortality with a long-term survival of only 15%. Currently the majority of treatments for AML are cytotoxic drugs with poor specificity. In order to develop safer therapeutics and more effective drugs, better understanding of the mechanisms that underlie the disease are needed.

My research aims at understanding the epigenetic regulatory mechanisms of myelopoiesis and how they regulate multi-potency and differentiation. The importance of epigenetic regulation in myelopoiesis is demonstrated by the finding of mutation in several epigenetic regulating genes in acute myeloid leukemia (AML). To be able to interpret the abnormal epigenetic regulations in AML, it is essential to first characterize and understand the epigenetic regulation during normal myelopoiesis. We aim to identify epigenetic regulatory enzymes that are important to keep the cell in a multi-potent stage, regulate lineage choice and differentiation. Their contribution to AML development and maintenance is also  analyzed. 

Another focus is on enhancers and how they regulate the transcriptome during normal and malign myelopoiesis. A key component to cell identity is the enhancer activity and how they control cell specific transcriptome. We recently showed that DNA demethylation coincide with enhancer activity during granulopoiesis (Rönnerblad et al 2014 Blood). 

Our aims are to:

 1. Map how the epigenetic modifications that are connected to enhancers are disturbed in acute myeloid leukemic stem cells.

 2. Characterize the effect the deregulated epigenetic modifications have on enhancer activity and on the transcriptional program that creates and stabilize multi-potency.  

3. Identify key epigenetic factors that regulate enhancer activity and multi-potency in hematopoietic stem cells.

4. Investigate whether these epigenetic factors are deregulated in AML and how they contribute to the leukemic phenotype.

 5. Analyze the role of the identified epigenetic factors have in drug resistance.




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, et al
BLOOD 2017;129(7):E13-E25

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, et al
Blood 2017;129(7):e13-e25

Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease
Tobiasson M, Abdulkadir H, Lennartsson A, Katayama S, Marabita F, De Paepe A, et al
Oncotarget 2017;8(17):28812-28825

Distinct global binding patterns of the Wilms tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells
Ullmark T, Järvstråt L, Sandén C, Montano G, Jernmark-nilsson H, Lilljebjörn H, et al
Haematologica 2017;102(2):336-345

FANTOM5 CAGE profiles of human and mouse samples
Noguchi S, Arakawa T, Fukuda S, Furuno M, Hasegawa A, Hori F, et al
Scientific data 2017;4():170112-

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria
Quin Je, Bujila I, Chérif M, Sanou Gs, Qu Y, Vafa Homann M, et al
eLife 2017;6():-

The HDAC inhibitor valproate induces a bivalent status of the CD20 promoter in CLL patients suggesting distinct epigenetic regulation of CD20 expression in CLL in vivo
Scialdone A, Hasni Ms, Damm Jk, Lennartsson A, Gullberg U, Drott K
Oncotarget 2017;8(23):37409-37422

The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells
Nilsson Hj, Montano G, Ullmark T, Lennartsson A, Drott K, Järvstråt L, et al
Oncotarget 2017;8(50):87136-87150

Update of the FANTOM web resource: high resolution transcriptome of diverse cell types in mammals
Lizio M, Harshbarger J, Abugessaisa I, Noguchi S, Kondo A, Severin J, et al
Nucleic acids research 2017;45(D1):D737-D743

External signals shape the epigenome
Lennartsson A
Genome biology 2016;17():18-

Mutations in histone modulators are associated with prolonged survival during azacitidine therapy
Tobiasson M, Mclornan Dp, Karimi M, Dimitriou M, Jansson M, Ben Azenkoud A, et al
Oncotarget 2016;7(16):22103-15

EpiFactors: a comprehensive database of human epigenetic factors and complexes
Medvedeva Ya, Lennartsson A, Ehsani R, Kulakovskiy Iv, Vorontsov Ie, Panahandeh P, et al
Database : the journal of biological databases and curation 2015;2015():bav067-

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

Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors
Lennartsson A, Arner E, Fagiolini M, Saxena A, Andersson R, Takahashi H, et al
Epigenetics & chromatin 2015;8():55-

Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells
Fantom Consortium, Joshi A, Pooley C, Freeman Tc, Lennartsson A, Babina M, et al

The Roles of SNF2/SWI2 Nucleosome Remodeling Enzymes in Blood Cell Differentiation and Leukemia
Prasad P, Lennartsson A, Ekwall K

Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells
Arner E, Daub Co, Vitting-seerup K, Andersson R, Lilje B, Drabløs F, et al
Science (New York, N.Y.) 2015;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-

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, et al
Blood 2014;123(17):e79-89

An atlas of active enhancers across human cell types and tissues
Andersson R, Gebhard C, Miguel-escalada I, Hoof I, Bornholdt J, Boyd M, et al
Nature 2014;507(7493):455-461

A promoter-level mammalian expression atlas
Riken Pmi Clst Dgt, Fantom Consortium, Forrest Arr, Kawaji H, Rehli M, Baillie Jk, et al
NATURE 2014;507(7493):462-70

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, et al
Epigenetics 2014;9(8):1108-19

High-throughput transcription profiling identifies putative epigenetic regulators of hematopoiesis
Prasad P, Rönnerblad M, Arner E, Itoh M, Kawaji H, Lassmann T, et al
Blood 2014;123(17):e46-57

microRNA-34b/c on chromosome 11q23 is aberrantly methylated in chronic lymphocytic leukemia
Deneberg S, Kanduri M, Ali D, Bengtzen S, Karimi M, Qu Y, et al
Epigenetics 2014;9(6):910-7

The DEK oncoprotein binds to highly and ubiquitously expressed genes with a dual role in their transcriptional regulation
Sandén C, Järvstråt L, Lennartsson A, Brattås Pl, Nilsson B, Gullberg U
Molecular cancer 2014;13():215-

Allele-specific programming of Npy and epigenetic effects of physical activity in a genetic model of depression
Melas Pa, Lennartsson A, Vakifahmetoglu-norberg H, Wei Y, Åberg E, Werme M, et al
Translational psychiatry 2013;3():e255-

Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR
Sandén C, Ageberg M, Petersson J, Lennartsson A, Gullberg U
BMC cancer 2013;13():440-

Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells
Vidovic K, Ullmark T, Rosberg B, Lennartsson A, Olofsson T, Nilsson B, et al
Leukemia research 2013;37(10):1341-9

Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression
Melas Pa, Rogdaki M, Lennartsson A, Bjork K, Qi Hs, Witasp A, et al

Epigenetic alterations related to early life stressful events
Lennartsson A

Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks
Deneberg S, Guardiola P, Lennartsson A, Qu Y, Gaidzik V, Blanchet O, et al
BLOOD 2011;118(20):5573-82

Wilms' tumor gene 1 protein represses the expression of the tumor suppressor interferon regulatory factor 8 in human hematopoietic progenitors and in leukemic cells
Vidovic K, Svensson E, Nilsson B, Thuresson B, Olofsson T, Lennartsson A, et al
LEUKEMIA 2010;24(5):992-1000

Histone modification patterns and epigenetic codes
Lennartsson A, Ekwall K

The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
Riken Omics Sci Ctr, Fantom Consortium, Suzuki H, Forrest Arr, Van Nimwegen E, Daub Co, et al
NATURE GENETICS 2009;41(5):553-62

All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBP beta and C/EBP epsilon to the BPI promoter
Lennartsson A, Vidovic K, Pass Mb, Cowland Jb, Gullberg U

Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein
Canny G, Cario E, Lennartsson A, Gullberg U, Brennan C, Levy O, et al

A murine antibacterial ortholog to human bactericidal/permeability-increasing protein (BPI) is expressed in testis, epididymis, and bone marrow
Lennartsson A, Pieters K, Vidovic K, Gullberg U

Bactericidal Permeability-increasing protein (BPI), a potentially important facet of innate immunity in intestinal epithelial cells
Canny Go, Lennartsson A, Levy O, Gullberg U, Doster R, Colgan Sp
FASEB JOURNAL 2005;19(4):A498-A498

Biosynthetic profiles of neutrophil serine proteases in a human bone marrow-derived cellular myeloid differentiation model
Garwicz D, Lennartsson A, Jacobsen Sew, Gullberg U, Lindmark A
HAEMATOLOGICA 2005;90(1):38-44

The proximal promoter of the human cathepsin G gene conferring myeloid-specific expression includes C/EBP, c-myb and PU.1 binding
Lennartsson A, Garwicz D, Lindmark A, Gullberg U
GENE 2005;:193-202

AML-1, PU.1, and Sp3 regulate expression of human bactericidal/permeability-inereasing protein
Lennartsson A, Pieters K, Ullmark T, Vidovic K, Gullberg U

A murine orthologue to human bactericidal/permeability increasing protein (BPI) is expressed in bone marrow, testis, and epididymis and possesses antibacterial activity towards gram-negative bacteria.
Lennartsson A, Pieters K, Vidovic K, Gullberg U
BLOOD 2003;102(11):275A-275A

Myeloid expression of the BPI (bactericidal permeability increasing protein) gene is regulated by AML1, Sp3, PU.1and C/EBP
Lennartsson A, Pieters K, Vidovic K, Gullberg U

Myeloid expression of the BPI (bactericidal/permeability increasing protein) gene is regulated by AML1 and C/EBP.
Lennartsson A, Pieters K, Vidovic K, Gullberg U
BLOOD 2002;100(11):246A-246A

Characterisation of the proximal promoter of human cathepsin G.
Lennartsson A, Gullberg U
BLOOD 2001;98(11):128B-128B

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