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P07.01 The potential role of extracellular vesicle-derived small RNAS in AML research as non-invasive biomarker
  1. L Li1,
  2. V Mussack2,
  3. A Görgens3,
  4. E Pepeldjiyska1,
  5. AS Hartz1,
  6. H Aslan1,
  7. E Rackl1,
  8. A Rank4,
  9. J Schmohl5,
  10. MW Pfaffl2 and
  11. H Schmetzer1
  1. 1Immune-Modulation, Medical Department III, University Hospital of Munich, München, Germany
  2. 2Department of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich, München, Germany
  3. 3Department of Laboratory Medicine, Division of Biomolecular and Cellular Medicine, Karolinska Institutet, Stockholm, Sweden
  4. 4Department of Hematology and Oncology, University Hospital of Augsburg,, Augsburg, Germany
  5. 5Department of Hematology and Oncology, Hospital of Stuttgart, Stuttgart, Germany


Background Antileukemic responses of immune reactive cells in AML-patients need to be improved. Combinations of blast-modulatory kitM (GM-CSF+PGE1) (vs control) convert myeloid blasts into dendritic cells of leukemic origin (DCleu), that effectively activate immune-cells against leukemic blasts. DC-derived EVs express molecules and carry nucleic acids (eg. miRNA) with immune regulatory functions.

Materials and Methods 1) DC/DCleu-generation of blast containing AML patients‘ (n=5) and of healthy volunteers(n=5) whole blood (WB) with kit M; 2) T-cell enriched mixed lymphocyte culture (MLC) with kit- vs un-treated WB; 3) antileukemic functional assays; 4) Sequencing of EV-derived miRNA from culture supernatants; 5) Qualitative/quantitative characterization of (leukemia/healthy) supernatant derived EVs and EV derived miRNAs as biomarkers.

Results 1) kitM increased significantly frequencies of (mature) DC/DCleu compared to untreated WB without induction of blasts’ proliferation. 2) kitM treated vs untreated WB increased significantly activated (leukemia-specific) cells of the adaptive and innate immune system after T cell-enriched MLC. 3a) EVs were qualitatively and quantitatively different in DC/MLC culture supernatants compared control as well as 3b) in kitM treated vs untreated healthy and AML samples. 3c) Different EV derived miRNAs were up- or downregulated in DC/MLC culture supernatants.

Conclusions These findings contribute to understand the unique/functional role of (leukemic derived) DCs to improve antileukemic immune responses, with respect to the role of EVs/EV derived miRNA and to potentially deduce new EV derived biomarkers.

Disclosure Information L. Li: None. V. Mussack: None. A. Görgens: None. E. Pepeldjiyska: None. A.S. Hartz: None. H. Aslan: None. E. Rackl: None. A. Rank: None. J. Schmohl: None. M.W. Pfaffl: None. H. Schmetzer: None.

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