Retained functional normal and preleukemic HSCs at diagnosis are associated with good prognosis in DNMT3AmutNPM1mut AMLs

Research output: Contribution to journalResearch articleContributedpeer-review


  • Elisa Donato - , German Cancer Research Center (DKFZ) (Author)
  • Nadia Correia - , German Cancer Research Center (DKFZ) (Author)
  • Carolin Andresen - , German Cancer Research Center (DKFZ) (Author)
  • Darja Karpova - , German Cancer Research Center (DKFZ) (Author)
  • Roberto Würth - , German Cancer Research Center (DKFZ) (Author)
  • Corinna Klein - , German Cancer Research Center (DKFZ) (Author)
  • Markus Sohn - , German Cancer Research Center (DKFZ) (Author)
  • Adriana Przybylla - , German Cancer Research Center (DKFZ) (Author)
  • Petra Zeisberger - , German Cancer Research Center (DKFZ) (Author)
  • Kathrin Rothfelder - , University of Tübingen (Author)
  • Helmut Salih - , University of Tübingen (Author)
  • Halvard Bonig - , University Hospital Frankfurt (Author)
  • Sebastian Stasik - , Department of Medical Biology, Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Christoph Röllig - , Department of Medical Biology, Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Anna Dolnik - , Charité – Universitätsmedizin Berlin (Author)
  • Lars Bullinger - , Charité – Universitätsmedizin Berlin, German Cancer Consortium (DKTK) partner site Berlin (Author)
  • Frank Buchholz - , University Cancer Centre, Chair of Medical Systems Biology, Department of Medical Biology, German Cancer Consortium (Partner: DKTK, DKFZ), University Hospital Carl Gustav Carus Dresden, National Center for Tumor Diseases (NCT) Dresden, German Cancer Research Center (DKFZ), Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Christian Thiede - , Department of Medical Biology, Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Daniel Hübschmann - , German Cancer Research Center (DKFZ) (Author)
  • Andreas Trumpp - , German Cancer Research Center (DKFZ) (Author)


Acute myeloid leukemia (AML) is a heterogeneous disease characterized by high rate of relapse and mortality. Current chemotherapies whilst successful in eradicating blasts, are less effective in eliminating relapse-causing leukemic stem cells (LSCs). Although LSCs are usually identified as CD34+CD38- cells, there is significant heterogeneity in surface marker expression, and CD34- LSCs exist particularly in NPM1mut AMLs. By analyzing diagnostic primary DNMT3AmutNPM1mut AML samples, we suggest a novel flow cytometry sorting strategy particularly useful for CD34neg AML subtypes. To enrich for LSCs independently of CD34 status, positive selection for GPR56 and negative selection for NKG2D ligands are used. We show that the functional reconstitution capacity of CD34- and CD34+ LSCs as well as their transcriptomes are very similar which support phenotypic plasticity. Furthermore, we show that although CD34+ subpopulations can contain next to LSCs also normal and/or preleukemic hematopoietic stem cells (HSCs), this is not the case in CD34-GPR56+NKG2DL- enriched LSCs which thus can be isolated with high purity. Finally, we show that patients with AML, who retain at the time of diagnosis a reserve of normal and/or preleukemic HSCs in their bone marrow able to reconstitute immunocompromised mice, have significantly longer relapse-free and overall survival than patients with AML in whom functional HSCs are no longer detectable.


Original languageEnglish
Pages (from-to)1011-1018
Number of pages8
JournalBlood advances
Issue number6
Publication statusPublished - 28 Mar 2023

External IDs

PubMed 36453648
PubMedCentral PMC10036514
Scopus 85152118327
Mendeley 7ddfec6e-70ff-3851-8cbd-dc4c60623b50
WOS 000974295900001



  • Acute myelogenous leukemia, Acute myeloid-leukemia, Expression, Marker, Nucleophosmin, Stem-cells