Hong Qian group – Leukemia niche

Our mission on research and education is to understand the role of mesenchymal niche in leukemia and tissue regeneration with the ultimate goal of identifying novel therapeutic strategies to improve treatment outcome in patients. The research group aims to build and nourish the niche for the team members to grow, while creating a supportive niche for our research projects.

Hong Qian research group are standing in an open shaft through the floors of a building
Photo: Amalia Kewenter

The main challenge for successful treatment of myeloid malignancies, particularly, acute myeloid leukemia (AML) has been drug resistance resulting in treatment failure, relapse and leukemia progression, which ultimately leads to death. Thus, there is a great need for more effective therapies. Recent studies have suggested that the drug resistance is attributed to the persistence of leukemia-initiating stem cells (LSCs). There is increasing evidence indicating that LSC persistence is due to the protection by bone marrow (BM) microenvironment, the so-called niche. Thus, targeting the BM niche may offer new therapeutic opportunities to improve the efficacy of current therapy for leukemia. However, so far, little is known about the critical molecular pathways mediating the niche interactions with LSCs and contributing to disease progression.

Current research focus

Our current research focus is on understanding BM niche contribution to the development of myeloid leukemia including chronic myeloid leukemia (CML) and AML and identify the key molecular pathways impacting the disease development and treatment outcome. We plan to achieve this by characterizing leukemia niche in patients and mice and functionally evaluate the impact of the dysregulated factors on the LSCs. The long-term goal is to identify the niche components that can serve as novel therapeutic targets and prognostic markers for myeloid leukemia.

Mesenchymal stem cells (MSCs) play an important role in maintaining HSC niche homeostasis and remodeling leukemia niche. Therefore, deciphering the role of the MSCs in leukemia development is one of our research priorities.

Group leader

Hong Qian

Group Leader. Dr.

Hong Qian was recruited to Karolinska Institutet as an Assistant Professor in 2012. She received a Ph.D. degree in Stem Cell Biology from Lund University, Sweden (2007) and did a postdoc at Department of Clinical and Experimental Medicine, Linköping University, Sweden (2008-2011).

 

Group members

Marja Ekblom

MD, PhD, Professor Emerita in Hematology

Dr. Marja Ekblom is Professor, Emerita in Hematology in the Department of Molecular Hematology, Lund University. She has worked in Skåne University Hospital as a senior hematologist with a special focus of chronic myeloid leukemia. Her preclinical research focus has been mainly in molecular hematology, including cell-cell/matrix interactions, in normal and malignant hematopoiesis.

Huan Cai

Postdoc

Huan Cai joined in Hong’s Group in January 2020 as a postdoc after his PhD study at University of Copenhagen. The current project focuses on understanding the role of bone marrow niche components, especially mesenchymal stem cells and extracellular matrix proteins like laminins, in the regulation of normal and malignant hematopoiesis.

Marcus Chang

Research assistant

Marcus Chang is a medical student at KI, works as a project student with a focus of risk niche factors for acute myeloid leukemia. In his free time, he likes to play table tennis and read books.

Elory Leonard

Research assistant

Elory Leonard is an Indonesian who recently obtained her master’s degrees from Erasmus Mundus International Joint Master’s Degree in Innovative Medicine at Ruprecht-Karls-Universität Heidelberg and Uppsala Universitet.

She has a keen interest and passion in molecular biology, drug discovery and development while also has had myriad of experiences working on oncologic (especially on hematologic malignancy: myelodysplastic syndrome and acute myeloid leukemia) and other clinical research in academic and pharmaceutical industry.  

Juan Pablo Medina

Affiliated to research

Juan Pablo Medina received his BSc degree in Biotechnology at Francisco de Vitoria University in 2015 and completed a MSc degree in Biomedical Technologies at Carlos III University in Madrid, Spain. He earned his PhD in Molecular Biosciences in 2021, developing his work in the field of cellular therapy and inflammatory joint diseases at Fundación Jiménez Díaz Hospital, in Madrid. He joined Qian’s group in September 2021.

Lakshmi Sandhow

Postdoc

Lakshmi Sandhow joined Hong Qian group as a PhD student in 2015 after receiving her master degree in Biomedicine from Karolinska Institutet. Her study focuses on mesenchymal niche contribution to normal and malignant hematopoiesis. In 2020, she received her PhD in Medical Science and continue pursuing her scientific interest in leukemia niche as a postdoc in Hong Qian group.

Previous group members

  • Thibault Bouderlique, Postdoc, 2015-2017.
  • Sanchari Choudhury, Yuchen Gao, Leah Hernandez-Muñoz, Moeen Ud-din, Master students, 2019-2020.
  • Monika Dolinska, PhD student, 2014-2019.
  • Andranik Durguryan, Postdoc, 2013-2014.
  • Eleni Gelali, Johannis Klang, Alexandre Piccini, Master students, 2014- 2015.
  • Anne-Sofie Johansson, Senior Lab manager at HERM.
  • Makoto Kondo, Postdoc, 2014-2017, currently assistant professor at College of Pharmacy, Utah, USA.
  • Elory Leonard and Jingyi Shen, Master students, 2020-2021.
  • Lakshmi Sandhow, PhD student, 2015-2020.
  • Pingnan Xiao, PhD student, 2012-2017, currently physician working at the first Affiliated Hospital of Zhejiang University, China.
  • Letian Yang, Summer student in 2021, currently at KTH, Stockholm.

 

Collaborations (major)

Sweden

  • Prof. Martin Bergö, BioNut, Karolinska Institutet
  • Prof. Anders Blomqvist, Linköping University
  • Prof. Marja Ekblom, Lund University
  • Prof. Qiang Pan-Hammarström, BioNut, Karolinska Institutet
  • Dr. Ulla Strömberg, Hematology Centrum, Uppsala University Hospital
  • Dr. Julian Walfridsson, Department of Medicine Huddinge, Karolinska Institutet

International

  • Nordic CML study group (NCMLSG)
  • Nordic society of pediatric hematology and oncology (NOPHO)
  • Prof. Nagahiro Minato, Kyoto University for MPN mouse model
  • Prof. Satu Mustjoki, Hematology Centrum, Helsinki University Hospital, Finland

Research support

  • Wallenberg Institutet for Regenerative Medicine (WIRM)
  • Karolinska Institutet Research foundation (KI fonder)
  • KI Funding for Doctoral Education (KID funding)
  • The Swedish Cancer Society (Cancerfonden)
  • The Swedish Research Council (Vetenskapsrådet)
  • The Swedish Childhood Cancer Society (Barncancerfonden)
  • Radiumhemmets Forskningsfonder (The Cancer Research Foundations of Radiumhemmet)
  • Felix Mindus bidrag till leukemiforskningen
  • Dr. Åke Olsson foundation for hematological research
  • Stiftelsen Clas Groschinskys Minnesfond
  • The Incyte Nordic Grant for Hematological Research
  • The Knut and Alice Wallenberg Foundation (KAW), PI: Qiang Pan-Hammarström, Co-PI: Petter Brodin, Lennart Hammarström, Hong Qian
  • The Blue Sky Research Grant for Innovative Cancer Research

Publications

View all publications in Web of Science

1. Progression of progenitor B-cell leukemia is associated with alterations of the bone marrow micro-environment
Åhsberg J, Xiao P, Okuyama K, Somasundaram R, Strid T, Qian H, Sigvardsson M
Haematologica 2020 03;105(3):e102-e106

2. Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy
Rudd SG, Tsesmetzis N, Sanjiv K, Paulin CB, Sandhow L, Kutzner J, Hed Myrberg I, Bunten SS, Axelsson H, Zhang SM, Rasti A, Mäkelä P, Coggins SA, Tao S, Suman S, Branca RM, Mermelekas G, Wiita E, Lee S, Walfridsson J, Schinazi RF, Kim B, Lehtiö J, Rassidakis GZ, Pokrovskaja Tamm K, Warpman-Berglund U, Heyman M, Grandér D, Lehmann S, Lundbäck T, Qian H, Henter JI, Schaller T, Helleday T, Herold N
EMBO Mol Med 2020 03;12(3):e10419

3. Distinct roles of mesenchymal stem and progenitor cells during the development of acute myeloid leukemia in mice
Xiao P, Sandhow L, Heshmati Y, Kondo M, Bouderlique T, Dolinska M, Johansson AS, Sigvardsson M, Ekblom M, Walfridsson J, Qian H
Blood Adv 2018 06;2(12):1480-1494

4. Sipa1 deficiency-induced bone marrow niche alterations lead to the initiation of myeloproliferative neoplasm
Xiao P, Dolinska M, Sandhow L, Kondo M, Johansson AS, Bouderlique T, Zhao Y, Li X, Dimitriou M, Rassidakis GZ, Hellström-Lindberg E, Minato N, Walfridsson J, Scadden DT, Sigvardsson M, Qian H
Blood Adv 2018 03;2(5):534-548

5. Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34+CD38- stem and progenitor cells in chronic myeloid leukemia
Dolinska M, Piccini A, Wong WM, Gelali E, Johansson AS, Klang J, Xiao P, Yektaei-Karin E, Strömberg UO, Mustjoki S, Stenke L, Ekblom M, Qian H
Biochem Biophys Res Commun 2017 08;490(2):378-384

6. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia
Giustacchini A, Thongjuea S, Barkas N, Woll PS, Povinelli BJ, Booth CAG, Sopp P, Norfo R, Rodriguez-Meira A, Ashley N, Jamieson L, Vyas P, Anderson K, Segerstolpe Å, Qian H, Olsson-Strömberg U, Mustjoki S, Sandberg R, Jacobsen SEW, Mead AJ
Nat Med 2017 Jun;23(6):692-702

7. A novel Lin-CD34+CD38- integrin α2- bipotential megakaryocyte-erythrocyte progenitor population in the human bone marrow
Wong WM, Dolinska M, Sigvardsson M, Ekblom M, Qian H
Leukemia 2016 06;30(6):1399-402

8. Molecular characterization of prospectively isolated multipotent mesenchymal progenitors provides new insight into the cellular identity of mesenchymal stem cells in mouse bone marrow
Qian H, Badaloni A, Chiara F, Stjernberg J, Polisetti N, Nihlberg K, Consalez GG, Sigvardsson M
Mol Cell Biol 2013 Feb;33(4):661-77

9. Primary mesenchymal stem and progenitor cells from bone marrow lack expression of CD44 protein
Qian H, Le Blanc K, Sigvardsson M
J Biol Chem 2012 Jul;287(31):25795-807

10. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells
Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Månsson R, Thoren LA, Ekblom M, Alexander WS, Jacobsen SE
Cell Stem Cell 2007 Dec;1(6):671-84

Oral presentations at international conferences

  • Pingnan Xiao gave an oral presentation at the at the 56th ASH Annual meeting, San Francisco, USA in 2014
  • Monika Dolinska gave an oral presentation at the 17th John Goldman CML conference, in 2015, Estoril, Portugal
  • Lakshmi Sandhow gave an oral presentation at ISSCR conference in 2015, in Stockholm, Sweden
  • Monika Dolinska gave an oral presentation at the ESH MSC conference, in 2017, Amsterdam
  • Makoto Kondo gave an oral presentation at the 58th ASH meeting, San Diego, USA. 2016
  • Lakshmi Sandhow gave an oral presentation at the ISSCR conference in June 2018, Melbourne, Australia

Student and postdoc Award

  1. The 56th ASH abstract achievement award to Pingnan Xiao in 2014
  2. The 58th ASH abstract achievement award to Makoto Kondo in 2016
  3. The Incyte Award to Monika Dolinska in 2018
  4. Travel award from International Stem Cell Research (ISSCR) to Lakshmi Sandhow in 2018
  5. Student award from Mayo Clinc for the 8th Mayo Clinic Symposium on Tumor Microenvironment and Cancer Therapeutics at Jacksonville, FL, USA, in 2018
  6. The Incyte Award for hematological research to Huan Cai, in 2021

Open positions

We always want to get in touch with talented potential co-workers. If you are interested in doing research within our group, as a degree project or as a researcher, please contact the group leader Hong Qian.