PO-46 - Influence of extracellular vesicles derived from AML patients on stem cells and their microenvironment

I Tzoran1, A Rebibo-Sabbah2, B Brenner2

  • 1Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus; Internal Medicine C, Rambam Health Care Campus; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology; Haifa, Israel.

Thrombosis Research
|May 11, 2016
PubMed
Abstract

Insights

Extracellular vesicles (EVs) from acute myeloid leukemia (AML) blast cells can influence hematopoietic stem cells (HSCs). Mesenchymal stem cells (MSCs) appear crucial for this process, highlighting a novel mechanism in AML progression.

Area of Science:

  • Hematology
  • Cell Biology
  • Cancer Research

Background:

  • Acute myeloid leukemia (AML) is a rapidly progressing cancer characterized by uncontrolled growth of leukemic blast cells.
  • Extracellular vesicles (EVs) are released by cells and carry surface proteins and antigens that reflect their cell of origin, including in pathological conditions like AML.

Purpose of the Study:

  • To investigate if bone marrow EVs from AML patients originate from blast cells.
  • To determine if these AML-derived EVs can affect hematopoietic stem cells (HSCs).
  • To explore this interaction within a co-culture system of HSCs and mesenchymal stem cells (MSCs), simulating a pseudo-natural microenvironment.

Main Methods:

  • Bone marrow samples were collected from AML patients and healthy controls at different disease stages.
  • EVs were characterized for concentration, origin, and protein expression using flow cytometry (FACS).
  • HSCs were isolated from cord blood and co-incubated with AML EVs in the presence or absence of MSCs, with EV internalization assessed by FACS-AMNIS and confocal microscopy. MicroRNA expression (mir-125b, mir-155) was analyzed via RT-PCR.

Main Results:

  • AML patients exhibited higher blast EV counts compared to controls and patients in remission.
  • Internalization of AML-derived EVs (CD117+/CD33+) into HSCs was confirmed, with EVs found within cell cytoplasm and nuclei.
  • Exposure to AML EVs, particularly in the presence of MSCs, showed a tendency to increase mir-125b and mir-155 expression in HSCs.

Conclusions:

  • Bone marrow EVs in AML patients are indeed derived from blast cells.
  • These EVs can influence the differentiation of naive stem cells through internalization.
  • Mesenchymal stem cells appear to play a significant role in mediating the effects of AML EVs on stem cells.

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