Abstract：
:Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes originate from leukemic blasts or from various normal cells in the bone marrow or other tissues is unknown. In the current study, we developed an AML PDX model in mice and studied the molecular cargo and immune cell effects of the AML PDX exosomes in parallel with the exosomes from plasma of the corresponding AML patients. Fully engrafted AML PDX mice produced exosomes with characteristics similar to those of exosomes isolated from plasma of the AML patients who had donated the cells for engraftment. The engrafted leukemic cells produced exosomes that carried human proteins and leukemia-associated antigens, confirming the human origin of these exosomes. Furthermore, the AML-derived exosomes carried immunosuppressive proteins responsible for immune cell dysfunctions. Our studies of exosomes in AML PDX mice serve as a proof of concept that AML blasts are the source of immunosuppressive exosomes with a molecular profile that mimics the content and functions of the parental cells.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Hong CS,Danet-Desnoyers G,Shan X,Sharma P,Whiteside TL,Boyiadzis Mdoi
10.1016/j.exphem.2019.07.005subject
Has Abstractpub_date
2019-08-01 00:00:00pages
60-66.e2eissn
0301-472Xissn
1873-2399pii
S0301-472X(19)30918-Xjournal_volume
76pub_type
杂志文章abstract：OBJECTIVE:A complete process for mass generation of megakaryocytes from hematopoietic stem cells under serum-free conditions has great clinical potential for rapid platelet reconstruction in thrombocytopenia patients. We have previously reported on the generation of an optimized serum-free medium (serum-free hematopoie...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.07.012
更新日期：2009-11-01 00:00:00
abstract：:Serum erythropoietin (Epo) levels are depressed in anemic AIDS patients relative to controls. The basis for abnormal regulation of Epo has not been defined. The hepatoma cell line Hep3B produces Epo in response to hypoxia and serves as a model for the study of Epo regulation. Hep3B cells are infectible with human immu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:Demineralized allogeneic bone matrix (DBM), implanted in muscle, induces the formation of an ossicle within which histologically recognizable hemopoietic tissue develops. Analyses of rabbit ossicle marrow in a methylcellulose culture system demonstrated the presence of committed hemopoietic precursors; colony-forming ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:Agar cultures of human bone marrow cells stimulated by cord plasma or irradiated cord blood feeder layers demonstrated the presence of a multilineage hemopoietic growth factor in cord blood. When bone marrow cultures stimulated with giant cell tumor-conditioned medium (GCT-CM) were supplemented with this cord blood-de...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:Two types of murine marrow adherent cells derived from Dexter cultures have been characterized. Exposure of C57B1/6J, ICR, or BDF1 mice to 1000 R x-ray 24 h prior to killing and establishment of liquid marrow cultures resulted in the growth of two types of adherent cells. A macrophage-like cell was phagocytic, nonspec...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：OBJECTIVE:Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of by...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.01.014
更新日期：2007-04-01 00:00:00
abstract：:We have attempted to evaluate in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on acute radiation hematopoietic injury in mice. BDF1 mice, irradiated with 7.5-Gy x-rays, were injected i.p. twice daily for 10 days with 10(5) U recombinant hum...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
abstract：:Despite its growing use as a marker of proliferation, the relationship between expression of the nuclear antigen Ki67 and other indices of proliferation in acute myelogenous leukemia (AML) has not been elucidated. In this study, short-term primary suspension cultures of human AML bone marrow cells were used to compare...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-12-01 00:00:00
abstract：OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.11.005
更新日期：2007-03-01 00:00:00
abstract：:The kinetics of cell turnover for myeloid/monocyte cells that form colonies in agar (GM-CFC) were measured through the progressive increase in their sensitivity to 313-nm light during a period of cell labeling with BrdCyd. Two components of cell killing with distinctly separate labeling kinetics revealed both the pres...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Haploinsufficiency of erythroid Krüppel-like factor (EKLF/KLF1) has been shown recently to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. I...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.03.004
更新日期：2018-07-01 00:00:00
abstract：:We have studied the effect of cortisone acetate (CA) on two important biological functions: (1) on NK cell-mediated cytotoxicity of B6D2F1 mice to T cell lymphoma, YAC-1 and (2) on hybrid resistance of mice to parental B6 bone marrow grafts. Results of our experiments have shown that 5 mg of CA administered i.p. was e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：:[3H]thymidine uptake by NFS-60 cells in microcultures was found to increase in a linear fashion with the increasing doses of purified recombinant human granulocyte colony-stimulating factor (rhG-CSF). Such increases were found neither with rhG-CSF samples pretreated with rabbit anti-rhG-CSF serum nor with other human ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：OBJECTIVES:To analyze the consequences of lymphocyte donations on lymphopoiesis in donors having previously undergone hematopoietic stem cell collection for allogeneic stem cell transplantation. METHODS:Repeated analysis of leukocyte subsets in the peripheral blood of 76 hematopoietic stem cell donors undergoing lymph...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.07.021
更新日期：2004-11-01 00:00:00
abstract：:Colony forming unit (CFU) assays were developed for feline granulocyte-macrophage (CFUGM), early erythroid (day 2 CFUE), and late erythroid (day 7 CFUE) colonies in methylcellulose medium. Feline CFUGM and both day 2 and day 7 CFUE were enhanced by feline macrophage conditioned medium and late CFUE often were intimate...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro. Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-02-01 00:00:00
abstract：:Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to ...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2015.04.011
更新日期：2015-07-01 00:00:00
abstract：:We have previously shown that CD33- CD34+ human marrow cells are capable of giving rise to colony-forming cells (CFC) in long-term marrow culture (LTMC) but are mainly depleted of progenitors that directly form colonies in semi-solid media. In contrast, the CD33+ CD34+ population contains most of the CFC but not the p...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:The osteoclast is a hematopoietic cell derived from CFU-GM and branches from the monocyte-macrophage lineage early during the differentiation process. The marrow microenvironment appears critical for osteoclast formation due to production of RANK ligand, a recently described osteoclast differentiation factor, by marro...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/s0301-472x(99)00061-2
更新日期：1999-08-01 00:00:00
abstract：:Recombinant human interleukin 6 (rhIL-6) was administered s.c. every 12 h at a daily dose of 10 micrograms/kg body weight to normal healthy mice. After 4 days the numbers of progenitor cells (erythroid burst-forming units, BFU-E and granulocyte-macrophage colony-forming cells, GM-CFC) were significantly increased (p l...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：OBJECTIVE:The aim of this study was the preclinical evaluation of imatinib mesylate (Gleevec, formerly STI571) in conjunction with arsenic trioxide (As2O3, Trisenox) for the treatment of chronic myelogenous leukemia (CML). MATERIALS AND METHODS:Tetrazolium-based cell line proliferation assays (MTT assays) were perform...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00836-6
更新日期：2002-07-01 00:00:00
abstract：:A right atrial catheter was implanted into 15 patients undergoing bone marrow transplantation as a treatment for acute leukemia. The catheter remained in position for 79 +/- 34 days. No catheter-related septicemia was observed. It appears that this catheter is helpful in supporting bone marrow transplant recipients. ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
abstract：OBJECTIVE:These studies were performed to test the hypothesis that DNMT1 is required for maintenance of DNA methylation and repression of the γ-globin gene in adult-stage erythroid cells. MATERIALS AND METHODS:DNMT1 levels were reduced by nucleofection of small interfering RNA targeting DNMT1 in chemical inducer of di...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2010.10.003
更新日期：2011-01-01 00:00:00
abstract：OBJECTIVE:The ABCG2 transporter has been identified as a determinant of the side population (SP) in murine bone marrow and a potential marker for primitive stem cells. To assess the potential of the SP phenotype and ABCG2 expression to identify stem cells in human umbilical cord blood (hUCB), we have examined directly ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.09.015
更新日期：2009-02-01 00:00:00
abstract：:Human umbilical cord blood (CB) appears to be an exciting new source of transplantable stem cells for a variety of clinical conditions. In this study, we have attempted to further characterize the primitive progenitors in CB. First we analyzed the effects of early-acting growth factors on blast cell colony formation f...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：OBJECTIVE:It is well known that hypoxic stress strongly enhances erythropoiesis, but the effect of hypoxia on erythroid progenitors has not been examined precisely. In the present study, using the erythropoietin-dependent cell line UT-7/Epo, which has characteristics of erythroid progenitors, we investigated a novel ro...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.01.013
更新日期：2005-05-01 00:00:00
abstract：OBJECTIVE:Hematopoietic stem cells (enriched in fraction of CD34+ cells) have the ability to regenerate hematopoiesis in all of its lineages, and this potential is clinically used in transplanting bone marrow or peripheral blood stem cells. Our objective was to assemble a suitable method for evaluating gene expression ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.006
更新日期：2006-07-01 00:00:00
abstract：:The tumor suppressor p53 is thought to play a role in megakaryocyte (MK) development. To assess the influence of the p53 regulatory pathway further, we studied the effect of RG7112, a small molecule MDM2 antagonist that activates p53 by preventing its interaction with MDM2, on normal megakaryocytopoiesis and platelet ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.11.012
更新日期：2014-02-01 00:00:00
abstract：:Increasing evidence points to endoglin (Eng), an accessory receptor for the transforming growth factor-β superfamily commonly associated with the endothelial lineage, as an important regulator of the hematopoietic lineage. We have shown that lack of Eng results in reduced numbers of primitive erythroid colonies as wel...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2012.06.007
更新日期：2012-10-01 00:00:00
abstract：:Rats made transiently neutropenic by intra-arterial administration of vinblastine (3 mg/kg) and infected with E. coli (6.02+/-0.45 X 10(8), per animal) have a mortality rate of 90% within 48 h post infection. Multiple transfusions of large numbers of granulocytes (harvested from Deca-Durabolin treated donor rats) prot...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
