Microvesicles microRNAs Reflect and Affect Progression of Acute Myeloid Leukemia and Could Serve As a Biomarker of Disease Dynamics

• Published in: Blood 2016-12, Vol.128 (22), p.1664-1664
• Main Authors: Tzoran, Inna, Rebibo-Sabbah, Annie, Brenner, Benjamin, Aharon, Anat
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.1664.1664

Background: Acute myeloid leukemia (AML) is characterized by rapid growth of abnormal blast cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Microvesicles (MVs) are shedding from various cells and express antigens reflecting their cellular origin. Our previous study has demonstrated a correlation between the level of MVs originating from blast cells (CD117+ MVs) in the peripheral blood and the amount of CD117 positive blast cells in the bone marrow (BM) at diagnosis and in remission (r=0.49, p=0.0025; r=0.6, p=0.01; respectively). Additional assessment of CD117 expression on MVs obtained at diagnosis in patients who died despite achieving a remission revealed significantly higher values compared to those found in patients who were alive at 3 years of follow-up (1.9 vs. 0.6; p=0.01). A similar trend was found in CD34 positive MVs (1.2 vs. 0.13; p=0.01). It has, therefore, been concluded that circulating MVs of AML patients might serve as a biomarker of leukemia progression. MVs also contain cytokines and micro-RNA (miRNA) that are critical for cell development, proliferation and apoptosis. MVs are the major transport vehicle for miRNAs, and serve as a unique mode of genetic exchange between cells. To this end, several studies have shown that cancer stem cells regulate tumor environment through MVs. The current study aimed to explore the potential role of MV miRNAs as a biomarker of disease progression in AML and to study MV effects on the bone marrow leukemic niche. Methods: Blood and bone marrow samples were collected from healthy controls and patients with AML at diagnosis and upon achievement of first remission. MV effects on the BM mesenchymal stem cells (BM-MSC) and endothelial cells were studied using confocal microscopy, migration and proliferation assays and the RT-PCR method. miRNA expression was screened by NanoString technology and validated by RT-PCR. Results: The study was approved by the Institutional Review Board of the Rambam Health Care Campus (Approval #0351-10). Blood and bone marrow samples were collected from 43 AML patients and 4 random healthy volunteers after obtaining written informed consent. Sixty seven percent of patients remained alive and achieved remission following induction chemotherapy about one month after the diagnosis. Co-incubation of fluorescent-labeled BM-MVs (CD33+/CD117+) of AML patients with unlabeled BM-MSC resulted in incorporation of >80% of MVs to the cells. Pati