Sören Lehmann group - Acute myeloid leukemia

Acute myeloid leukemia (AML) is a disease with an enormous unmet medical need. We aim to take on the challenges with AML through a translational approach aiming to increase our understanding of the epigenetic dysregulation in AML and develop this knowledge into better treatments and new tools for precision medicine. We integrate epigenetic data with genome wide multiomic data and drug sensitivity data to better understand how AML develops and how treatment should be improved.

Photo of Sören Lehmann's group
Photo of Sören Lehmann's group. Photo: Private

About our research

A major task for our group is to define how the AML epigenome is dysregulated in AML, how this leads to leukemia transformation and how this can be used for precision medicine and for improving the treatment of the disease. We currently focus on advanced integrated epigenetic analyses describing the higher order of chromatin and we also explore the role of long non-coding RNAs (lncRNAs) in AML.

To understand the epigenetic dysfunctions in AML in a more complex molecular perspective, we explore the interplay between the epigenome with the AML genome, transcriptome, proteome and drug sensitivity using genome wide multiomic characterization in large AML cohorts. We then use gene editing techniques such as CRISPR-Cas9 and dCas9 to individually validate molecular features that are most likely to be important for AML transformation and treatment. As AML cell populations are heterogenous we also study cell heterogeneity with a focus on epigenetic changes using several types of in single cell analyses.

We are especially interested in the epigenetic effects behind the synergism between azacytidine and venetoklax and we study this with a combination of epigenetic and proteomics studies. Using larger population-based cohorts, we also study the role of clonal hematopoeisis with focus on mutations in epigenetically regulating genes.

In addition to our epigenetic approach, we have a particular interest in therapy-related AML as well as acute promyelocytic leukemia that we study from an epidemiological as well as a molecular perspective.

Group leader

Soren Lehmann

Professor/senior physician
Hematologi
H7 Department of Medicine, Huddinge

Sören Lehmann is MD and has specialist degrees in hematology and internal medicine. He received his PhD in 2002 at Karolinska Institutet and was post doc at UCLA, Los Angeles in 2005 to 2006. Sören is full professor of hematology at Uppsala University since 2015. The Lehmann Group is situated both at Karolinska Institutet and at Uppsala University.

Sören is member of the steering committees of the Swedish AML Group, the Nordic AML Group and the HOVON International Steering Committee and chair of the Scientific Committee of the Nordic AML Group.

Group members

Elisabetta Cozzi

PhD student
Lehman
H7 Department of Medicine, Huddinge

Elisabetta Cozzi received her BSc in Biology from the University of Trieste in 2017 and earned her MSc degree in Molecular biotechnologies at the same University in 2019. Elisabetta joined Sören Lehmann's group in November 2020 as a PHD student. Her studies are focued on the understanding of the role of long non-coding RNAs for the development of AML as well as for the response to antileukemic substances.

Sofia Bengtzén

Affiliated to research
Lehman
H7 Department of Medicine, Huddinge

Sofia Bengtzén is laboratory technician with an additional degree in molecular biology and has worked in the hematology research laboratory in Huddinge since 1995. She is currently working as main responsible for biobanking in the Lehmann Group. She is also supporting many of the projects as a technician and a molecular biologist.

Anna Bohlin

Research nurse
Lehman
H7 Department of Medicine, Huddinge

Anna Bohlin is registered Nurse since 2002 and has a master degree in nursing. Anna has worked as a nurse at Norrlands University Hospital in Umeå and since 2006 at the Hematology Department at Karolinska University Hospital in Huddinge. At Karolinska, she has worked as a clinical nurse, as stem cell transplant coordinator and as a research nurse. Anna joined the group in 2018 as now works as a research nurse and a precision medicine nurse for AML. She is also affiliated to the myeloma group.

Xiangfu Zhong

Postdoctoral researcher
Lennartsson
H2 Department of Biosciences and Nutrition

Xiangfu Zhong joined in Lehmann’s Group in November 2019 as a bioinformatician. He received his PhD at University of Oslo, Norway. The current project focuses on understanding the epigenetics of acute myeloid leukemia, by analyzing and integrating epigenomics and transcriptomics data, such as ChIP-seq, RNA-seq and DNA methylation.

Members of Lehmann Group at Uppsala University

Albin Österroos

MD, PhD student

Department: Department of Medical Sciences, Uppsala University

Albin Österroos graduated from the Medicine Program at Uppsala University in 2014 and completed his medical internship (AT) in 2016. He currently works as a research resident physician (forskar-ST) in hematology and internal medicine at Akademiska University Hospital in Uppsala. He registered as a PhD student in the Lehmann group in Uppsala in 2016 with projects that aim at integrating patient data, preclinical research and novel sequencing tools to improve the molecular understanding of acute myeloid leukemia and its treatments.

Angelica Gamboa

Post-doc

Department: Department of Medical Sciences, Uppsala University

Angelica (Linda) Gamboa received her PhD 2021 at the University of Buenos Aires. Since 2022, she is post-doc in the Lehmann Group in Uppsala. She obtained her PhD within the lymphoid field and is now working with epigenetic characterization in AML, spanning from studies of histon marks by immunohistochemistry to ATAC-seq and HiC studies in AML.

Marcus Liew Littorin

MD, PhD student

Department: Department of Medical Sciences, Örebro University

Markus Liew Littorin graduated from the Medicine Program in 2016 and is a clinical fellow in hematology at Örebro University Hospital. Marcus joined the group in 2022.

Former members

  • Anne Neddermeyer. PhD student
  • Kingkamon Junkulu, Post-doc
  • Anna Eriksson, Post-doc
  • Linda Arngården, Post-doc
  • Naomi Cook, Post-doc
  • My Björklund, Post-doc
  • Sylvain Marechal, Post-doc
  • Christer Nilsson, MD/PhD student
  • Huthayfa Mujahed, PhD student
  • Ying Qu, PhD student
  • Dina Ali, PhD student
  • Stefan Deneberg, MD/PhD student

Ongoing collaborations

  • Andreas Lennartsson, KI
  • Olli Kallioniemi, KI
  • Janne Lehtiö, KI
  • Pär Nordlund, KI
  • Chung Chau Hon, RIKEN Institute, Japan
  • Seichi Ogawa, University of Kyoto, Japan
  • Ulf Landegren, UU
  • Gunnar Juliusson, University of Lund
  • Martin Höglund, UU
  • Nordic AML Group (Gjertsen, Mönch-Thielgaard, Kontro)

Research support

  • Swedish Cancer Foundation
  • Swedish Research Council (VR)
  • Swedish Foundation for Strategic Research (SSF)
  • Knut and Alice Wallenberg Foundation (KAW)
  • The Cancer Society in Stockholm
  • Stockholm County Council (ALF)
  • Lions Foundations
  • Selanders Foundations

Selected publications

Characterization of therapy-related acute myeloid leukemia: increasing incidence and prognostic implications. Nilsson C, Linde F, Hulegårdh E, Garelius H, Lazarevic V, Antunovic P, Cammenga J, Deneberg S, Eriksson A, Jädersten M, Björkvall CK, Möllgård L, Wennström L, Ölander E, Höglund M, Juliusson G, Lehmann S. Haematologica. 2022 Aug 25. doi:10.3324/haematol.2022.281233.

Ultra-sensitive monitoring of leukemia patients using superRCA mutation detection assays.Chen L, Eriksson A, Weström S, Pandzic T, Lehmann S, Cavelier L, Landegren U Nat Commun. 2022 Jul 12;13(1):4033.

A risk score based on real-world data to predict early death in acute promyelocytic leukemia. Österroos A, Maia T, Eriksson A, Jädersten M, Lazarevic V, Wennström L, Antunovic P, Cammenga J, Deneberg S, Lorenz F, Möllgård L, Uggla B, Ölander E, Aguiar E, Trigo F, Höglund M, Juliusson G, Lehmann S. Haematologica. 2022 Jul 1;107(7):1528-1537.

The transcriptome-wide landscape of molecular subtype-specific mRNA expression profiles in acute myeloid leukemia. Mou T, Pawitan Y, Stahl M, Vesterlund M, Deng W, Jafari R, Bohlin A, Österroos A, Siavelis L, Bäckvall H, Erkers T, Kiviluoto S, Seashore-Ludlow B, Östling P, Orre LM, Kallioniemi O, Lehmann S, Lehtiö J, Vu TN. Am J Hematol. 2021 May 1;96(5):580-588.

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 Feb 23;5(4):1003-1016.

Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia. Österroos A, Björklund M, Eriksson A, Lindberg J, Nilsson C, Mareschal S, Rantalainen M, Grönberg H, Lehmann S. Blood Cancer J. 2020 Jun 11;10(6):67. doi: 10.1038/s41408-020-0332-3.

AML Displays Increased CTCF Occupancy Associated to Aberrant Gene Expression and Transcription Factor Binding. Mujahed H, Miliara S, Neddermeyer AH, Bengtzen S, Nilsson C, Deneberg S, Cordeddu L, Ekwall K, Lennartsson A, Lehmann S. Blood. 2020 Jul 16;136(3):339-352

Real-world data on treatment patterns and outcomes of hypomethylating therapy in patients with newly diagnosed acute myeloid leukaemia aged ≥ 60 years. Österroos A, Eriksson A, Antunovic P, Cammenga J, Deneberg S, Lazarevic V, Lorenz F, Möllgård L, Derolf ÅR, Uggla B, Wennström L, Ölander E, Höglund M, Juliusson G, Lehmann S. Br J Haematol. 2020 Apr;189(1):e13-e16.

Hypo, Hyper, or Combo: new paradigm for treatment of acute myeloid leukemia in older people. Juliusson G, Höglund M, Lehmann S. Haematologica 2020 Jan 31;105(2):249-251

Allele-specific DNA methylation is increased in cancers and its mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs. Do C, Dumont E, Salas M, Castano A, Mujahed H, Maldonado H, Singh A, Lehmann S, Christiano AM, Madhavan S, Nagy PL, Green P, Ilsey N, Feinman R, Trimble C, Marder K, Honig L, Monk C, Goy A, Chow K, Goldlust S, Kaptain G, Siegel D and Tycko B. Genome Biol 2020 Jun 29;21(1):153

Acute myeloid leukemia during twenty years – improved survival of males 50-75 years old. Juliusson G, Hagberg O, Lazarevic V, Ölander E, Antunovic P, Cammenga J, Wennström L, Möllgård L, Brune M, Jädersten M, Deneberg S, Lehmann S, Derolf Å, Höglund M. Blood 2020. Oct 31;134(18):1558-1561.

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting. Nilsson C, Hulegårdh E, Garelius H, Möllgård L, Brune M, Wahlin A, Lenhoff S, Frödin U, Remberger M, Höglund M, Juliusson G, Stockelberg D, Lehmann S. Biol Blood Marrow Transplant. 2019: S1083-8791(19)30363-5.

Expression levels of long non-coding RNAs are prognostic for AML outcome. Mer AS, Lindberg J, Nilsson C, Klevebring D, Wang M, Grönberg H, Lehmann S, Rantalainen M. . J Hematol Oncol. 2018 Apr 7;11(1):52.

Development and Validation of a Novel RNA Sequencing-Based Prognostic Score for Acute Myeloid Leukemia. Wang M, Lindberg J, Klevebring D, Nilsson C, Lehmann S, Grönberg H, Rantalainen M. J Natl Cancer Inst. 2018 Oct 1;110(10):1094-1101

Bone marrow stroma cells derived from mononuclear cells at diagnosis as a source of germline control DNA for determination of somatic mutations in acute myeloid leukemia. Mujahed H, Jansson M, Bengtzén S, Lehamnn S. Blood Cancer J. 2017 Oct 6;7(10):e616

Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling. Wang M, Lindberg J, Klevebring D, Nilsson C, Mer AS, Rantalainen M, Lehmann S*, Grönberg H*. Leukemia. 2017 Oct;31(10):2029-2036.

Early death rates remain high in high-risk APL: update from the Swedish Acute. Leukemia Registry 1997-2013. Lehmann S, Deneberg S, Antunovic P, Rangert-Derolf Å, Garelius H, Lazarevic V, Myhr-Eriksson K, Möllgård L, Uggla B, Wahlin A, Wennström L, Höglund M, Juliusson G. Leukemia. 2017 Jun;31(6):1457-1459.

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 Feb 16;129(7):e13-e25.

An open-label phase I dose-finding study of APR-246 in hematological malignancies. Deneberg S, Cherif H, Lazarevic V, Andersson PO, von Euler M, Juliusson G, Lehmann S. Blood Cancer J. 2016 Jul 15;6(7):e447

Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry. Hulegårdh E, Nilsson C, Lazarevic V, Garelius H, Antunovic P, Rangert Derolf Å, Möllgård L, Uggla B, Wennström L, Wahlin A, Höglund M, Juliusson G, Stockelberg D, Lehmann S. Am J Hematol. 2015 Mar;90(3):208-14.

Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landén M, Höglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Grönberg H, Hultman CM, McCarroll SA. N Engl J Med. 2014 Dec 25;371(26):2477-87.

Targeting p53 in Vivo: A First-in-Human Study With p53-Targeting Compound APR-246 in Refractory Hematologic Malignancies and Prostate Cancer. Lehmann S, Bykov VJ, Ali D, Andrén O, Cherif H, Tidefelt U, Uggla B, Yachnin J, Juliusson G, Moshfegh A, Paul C, Wiman KG, Andersson PO. J Clin Oncol. 2012 Oct 10;30(29):3633-9.)

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, Karimi M, Bengtzén S, Nahi H, Uggla B, Tidefelt U, Höglund M, Paul C, Ekwall K, Döhner K, Lehmann S. Blood. 2011 Nov 17;118(20):5573-82.