Abstract：
OBJECTIVE:Haplotype-mismatched CD34(+) selected allogeneic stem cell transplantation (HASCT) has been described as a therapeutic option for patients with acute myeloid leukemia. The success of this regimen is based mainly on natural killer (NK) cell-mediated antileukemia effects. MATERIALS AND METHODS:We prospectively investigated NK-cell (CD56(+)/CD3(-)) reconstitution, including expression of antileukemia effector molecules in patients undergoing HASCT. RESULTS:Although absolute NK-cell numbers rapidly increased, their phenotype notably differed compared to healthy controls. In fact, the "effector" CD56(dim) subset was significantly reduced, as was the NKG2D expression on "regulatory" CD56(bright) cells. Perforin was completely absent on NK cells in one-third of patients. The expression of Fas-ligand (Fas-L) on NK cells as well as soluble Fas-L and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plasma levels were also significantly lower after HASCT. In contrast, expression of TRAIL on CD56(dim) cells and interleukin-15 plasma levels were upregulated. Because the death rate due to relapse or infectious complications was high in the initial phase of the trial, subsequent patients received an adoptive infusion of donor NK cells followed by interleukin-2 in vivo in order to augment NK-cell function. This led to a distinct upregulation of perforin and Fas-L on the CD56(dim) subset accompanied by increased NK-cell cytotoxicity in vitro. CONCLUSION:The phenotype of reconstituting NK cells after HASCT is significantly altered. Whether the clinical outcomes of patients undergoing this regimen can be improved by a cytokine-based modulation of NK-cell activity needs to be determined.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Schulze A,Schirutschke H,Oelschlägel U,Schmitz M,Füssel M,Wassmuth R,Ehninger G,Bornhäuser M,Platzbecker Udoi
10.1016/j.exphem.2007.12.006subject
Has Abstractpub_date
2008-04-01 00:00:00pages
378-89issue
4eissn
0301-472Xissn
1873-2399pii
S0301-472X(07)00696-0journal_volume
36pub_type
临床试验,杂志文章abstract：OBJECTIVE:We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning. METHODS:Nonmyeloablative conditioning consisted of 2 Gy total-body irradiation+/-flud...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(03)00201-7
更新日期：2003-10-01 00:00:00
abstract：:The presence of granulocyte colony-stimulating factor receptor (G-CSFR) in CD34+ hematopoietic progenitors is demonstrated by flow cytometry. Cord blood mononuclear cells (MNCs) contain about 1.09 +/- 0.2% CD34+ cells, 0.32 +/- 0.1% CD34+/G-CSFR+ (G-CSFR+) cells, and 0.77 +/- 0.1% CD34+/G-CSFR- (G-CSFR-) cells. The co...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Acute myeloid leukemia (AML) develops when there is a block in differentiation and uncontrolled proliferation of myeloid precursors, resulting in bone marrow failure. AML is a clinically, morphologically, and genetically heterogeneous disease, and biological differences between adult and childhood AML have been identi...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2017.06.007
更新日期：2017-10-01 00:00:00
abstract：:Cholinergic toxicity of organophosphate insecticides is regarded as the principal health hazard associated with both human and animal exposures. Recent studies indicate that these pesticides may have important effects on both the immune and hematopoietic systems. In the present study, human bone marrow cells were expo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:Progress of age-related hematopoietic diseases such as myelodysplastic syndrome has previously been linked to enhanced levels of reactive oxygen species (ROS). Uncoupling protein 2 (UCP2) was found to reduce mitochondrial ROS production through uncoupling of the respiratory chain. The impact of UCP2 loss and elevated ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.08.003
更新日期：2016-11-01 00:00:00
abstract：:We performed the present study to define the in vitro hemopoietic activity of murine recombinant (r) granulocyte colony-stimulating factor (G-CSF) using murine hemopoietic culture systems of normal bone marrow cells, fetal liver cells, and spleen cells of 5-fluorouracil (FU)-treated mice. Recombinant G-CSF supported o...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:In this study, we have used the sublethally irradiated rat as a model to examine the relationship between platelet count and the plasma level of megakaryocyte growth-promoting activity (Meg-GPA) assayed in vitro. Meg-GPA of irradiated rats whose platelet counts were maintained by platelet transfusions was compared to ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:We evaluated the expansion capacity of untreated and 5-fluorouracil (5-FU)-resistant peripheral blood stem cells (PBSC) after 7-day incubation with interleukin-1 (IL-1) plus IL-3 plus stem cell factor (SCF) or with medium alone. We found a significant increase in the proportion of CD34+ cells in the PBSC fraction resi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：OBJECTIVE:The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex netw...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.02.009
更新日期：2008-07-01 00:00:00
abstract：OBJECTIVE:The mechanism for anagrelide's potent platelet lowering activity in human subjects is not well defined. Studies related to anagrelide function have been hampered by its lack of activity in nonhuman primates and water insolubility. In an effort to define the mechanism whereby anagrelide exerts its therapeutic ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00742-1
更新日期：2001-12-01 00:00:00
abstract：:An increasing amount of data provides strong evidence for the complex multifactorial control of primary hemopoietic functions. Here we present a new multicellular functional unit, the Hematon, isolated from the light-density floating fraction of normal human bone marrow (BM) aspirates. The Hematon is organized in a co...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：OBJECTIVE:Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. MATERIALS AND METHODS:In this study, histopathological classification of 490 MPN cases was...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.07.005
更新日期：2009-10-01 00:00:00
abstract：:The history of clonal hematopoiesis (CH) research is punctuated by several seminal discoveries that have forged our understanding of cancer development. The clever application of the principle of random X-chromosome inactivation (XCI) in females led to the development of the first test to identify clonal derivation of...
journal_title：Experimental hematology
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.exphem.2020.01.008
更新日期：2020-03-01 00:00:00
abstract：OBJECTIVE:Many clinical gene therapy trials have described poor engraftment of retrovirally transduced CD34(+) cells. Because engraftment is dependent upon successful homing of graft cells to the bone marrow (BM), we examined whether retroviral-mediated gene transfer (RMGT) induces a homing defect in CD34(+) cells. ME...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.12.014
更新日期：2006-04-01 00:00:00
abstract：:The aberrant overexpression of Wilms tumor-1 (WT1) in acute myeloid leukemia (AML) plays an important role in blast cell survival by enhancing proliferation and inhibiting apoptosis. However, the mechanism underlying the overexpression of WT1 remains unclear. Here, we identified miR-193a (miR-193a-5p) and miR-600 targ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.02.001
更新日期：2018-05-01 00:00:00
abstract：:Initially described as an endogenous inhibitor of proteases, the tissue inhibitor of metalloproteinases 1 (TIMP-1) also displays cytokine-like functions. TIMP-1 is a soluble protein whose levels are increased under inflammatory conditions. We recently found that TIMP-1(-/-) mice have decreased bone marrow (BM) cellula...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.07.003
更新日期：2015-11-01 00:00:00
abstract：:Unlike cell lines, human hematopoietic stem cells (HSCs) are less efficiently transduced with HIV-1 vectors, potentially limiting this approach. To investigate which step (internalization, reverse transcription, nuclear transport, and integration) limits lentiviral transduction, we evaluated the kinetics of lentiviral...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2015.10.003
更新日期：2016-02-01 00:00:00
abstract：OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.07.017
更新日期：2004-11-01 00:00:00
abstract：:A single injection of > or =10 microg/kg PEG-rHuMGDF in mice causes a dose-dependent increase in circulating platelets beginning on day 3 and peaking on days 5-6. The mean platelet volume and platelet distribution width at doses > or =100 microg/kg initially increase in a dose-dependent fashion and later decrease. How...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(98)00012-5
更新日期：1999-01-01 00:00:00
abstract：:Adult hematological malignancies, such as acute myeloid leukemia, are thought to arise through the gradual acquisition of oncogenic mutations within long-lived hematopoietic stem cells (HSCs). Genomic analysis of peripheral blood DNA has recently identified leukemia-associated genetic mutations within otherwise health...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.08.004
更新日期：2019-09-01 00:00:00
abstract：:The ability to epigenetically reprogram differentiated somatic cells to pluripotency resulting in the discovery of induced pluripotent stem cells (iPSCs), has unlocked fundamental biologic insights into numerous genetic diseases. These insights have resulted from the key property of iPSCs to differentiate into all cel...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.01.002
更新日期：2019-03-01 00:00:00
abstract：:After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the developm...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2018.09.006
更新日期：2019-01-01 00:00:00
abstract：:Purified normal murine bone marrow-derived fibroblasts were shown to produce a factor that stimulates the in vitro growth of fibroblastic colony-forming unit (CFU-F) colonies. Conditioned medium from the purified fibroblasts (F-CM) also stimulated pure marrow fibroblasts themselves. Analysis of the F-CM detected the p...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-05-01 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：:Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.08.007
更新日期：2020-10-01 00:00:00
abstract：:Several prospective randomized trials in acute myelocytic leukemia (AML) documented a lower relapse rate with autologous bone marrow transplantation (ABMT) than with conventional chemotherapy. However, they also identified some transplant difficulties, such as failure to collect sufficient numbers of stem cells, slow ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00121-6
更新日期：1999-12-01 00:00:00
abstract：:Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Serum albumin has long been an essential supplement for ex vivo hematopoietic and immune cell cultures. However, serum albumin medium supplements represent a major source of biological contamination in cell cultures and often cause loss of cellular function. As serum albumin exhibits significant batch-to-batch variabi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.11.007
更新日期：2019-12-01 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
