DPP4+ exosomes in AML patients’ plasma suppress proliferation of hematopoietic progenitor cells
Autor: | Hal E. Broxmeyer, Michael Boyiadzis, Theresa L. Whiteside, Swathi Namburi, Chang-Sook Hong |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research Dipeptidyl Peptidase 4 medicine.medical_treatment Cell Exosomes Article 03 medical and health sciences 0302 clinical medicine Cell Line Tumor hemic and lymphatic diseases medicine Humans Cell Proliferation Serine protease Chemotherapy biology Chemistry Myeloid leukemia Hematology Hematopoietic Stem Cells medicine.disease Microvesicles In vitro Hematopoiesis Leukemia Myeloid Acute Haematopoiesis Leukemia 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research biology.protein |
Zdroj: | Leukemia |
ISSN: | 1476-5551 0887-6924 |
Popis: | Mechanisms by which acute myeloid leukemia (AML) interferes with normal hematopoiesis are under intense investigation. Emerging evidence suggests that exosomes produced by leukemia blasts suppress hematopoiesis. Exosomes isolated from AML patients' plasma at diagnosis significantly and dose-dependently suppressed colony formation of normal hematopoietic progenitor cells (HPC). Levels of HPC suppression mediated by exosomes of AML patients who achieved complete remission (CR) were significantly decreased compared to those observed at AML diagnosis. Exosomes from plasma of patients who had achieved CR but with incomplete cell count recovery (CRi) after chemotherapy suppressed in vitro colony formation as effectively as did exosomes obtained at AML diagnosis. Dipeptidylpeptidase4 (DPP4/CD26), a serine protease that cleaves select penultimate amino acids of various proteins, has been previously implicated in the regulation of hematopoiesis. DPP4 was carried by exosomes from AML plasma or leukemia cell lines. Leukemia exosomes which suppressed HSC colony formation had markedly higher DPP4 functional activity than that detected in the exosomes of normal donors. Pharmacological inhibition of DPP4 activity in AML exosomes reversed the effects of exosome-mediated myelosuppression. Reversing the negative effects of exosomes on AML hematopoiesis, and thus improving cell count recovery, might emerge as a new therapeutic approach to AML. |
Databáze: | OpenAIRE |
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