Abstract:
OBJECTIVE:To investigate the interaction of imatinib mesylate (IM) with the clinically relevant adenosine triphosphate-binding cassette efflux transporter MDR1 (ABCB1) in cells from patients with chronic myeloid leukemia (CML) and to explore whether inhibition of this transporter would improve IM's efficacy in the elimination of CML CD34(+) cells by increasing cell-associated drug accumulation. MATERIALS AND METHODS:Cells from newly diagnosed chronic-phase CML patients were harvested by leukapheresis and enriched to >95% CD34(+). Expression of the transporter gene MDR1 was performed by quantitative reverse transcription polymerase chain reaction. Interaction of IM with MDR1 was analyzed by substrate (rhodamine 123) displacement assay. Cell-associated levels of IM in CML CD34(+) cells were measured by high-pressure liquid chromatography. Intracellular phospho-CrkL levels, apoptosis in total CML CD34(+) cells and high-resolution tracking of cell division were assayed by flow cytometry. RESULTS:Measurements of cell-associated IM uptake showed significantly lower drug levels in CD34(+) cells, particularly the CD38(-) subpopulation, as compared to IM-sensitive K562 cells. MDR1 was expressed at low level and dye efflux studies demonstrated very little MDR1 activity in CML CD34(+) cells. Furthermore, combination treatment of primitive CML cells with IM and the MDR1 inhibitor PSC833 did not result in elevated cell-associated IM levels. Although we observed slightly enhanced cytostasis with IM when combined with PSC833, this was independent of BCR-ABL inhibition because no associated decrease in phospho-CrkL was observed. CONCLUSIONS:Our findings demonstrate that inhibition of MDR1 neither enhances the effect of IM against BCR-ABL activity, nor significantly potentiates IM's efficiency in eliminating primitive CML cells.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Hatziieremia S,Jordanides NE,Holyoake TL,Mountford JC,Jørgensen HGdoi
10.1016/j.exphem.2009.02.006subject
Has Abstractpub_date
2009-06-01 00:00:00pages
692-700issue
6eissn
0301-472Xissn
1873-2399pii
S0301-472X(09)00054-Xjournal_volume
37pub_type
杂志文章abstract::The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment is a rapidly evolving area of research. Normal HSC processes rely heavily on a complex communication network involving various marrow niches. Although leukemogenesis largely results from abnormal gene...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.07.001
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:All-trans retinoic acid (ATRA) has been used as the first-line therapy for patients with acute promyelocytic leukemia (APL). We previously reported that ATRA increased serum thrombopoietin (TPO) levels accompanied by thrombocytosis during ATRA therapy for APL. In this study, we investigated the mechanism of t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2003.10.009
更新日期:2004-01-01 00:00:00
abstract::Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-10-01 00:00:00
abstract:OBJECTIVE:Multipotent germline stem (mGS) cells derived from neonatal mouse testis, similar to embryonic stem (ES) cells, differentiate into various types of somatic cells in vitro and produce teratomas after inoculation into mice. In the present work, we examined mGS cells for hematopoietic progenitor potential in vit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.09.006
更新日期:2009-12-01 00:00:00
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:OBJECTIVE:Cyclosporine A (CsA), known as an effective immunosuppressive agent, is widely used in clinical fields. Mesenchymal stem cells may exert immunomodulatory effects on the immune system, but the exact mechanisms underlying them remain controversial. Here we investigated whether human adipose tissue-derived mesen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.10.009
更新日期:2011-02-01 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:OBJECTIVE:We have previously shown that nitric oxide (NO) is involved in the hydroxyurea-induced increase of gamma-globin gene expression in cultured human erythroid progenitor cells and that hydroxyurea increases NO production in endothelial cells via endothelial NO synthase (NOS). We have now expanded those studies t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.06.009
更新日期:2009-10-01 00:00:00
abstract::An 18-year-old male with severe aplastic anemia associated with hepatitis was prepared for bone marrow transplantation with cyclophosphamide (50 mg/kg/day) for 4 consecutive days. He then received 3.47 X 10(8) nucleated bone marrow cells per kilogram of body weight from his HL-A identical sister by intravenous infusio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::Adherent cells from mouse bone marrow have been shown to promote the in vitro growth of the AVRij-1 tumour cell line. The experiments presented here suggest that the adherent cells involved in this phenomenon are the progeny of bone marrow derived fibroblastoid colony forming units. The latter were characterized by me...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-04-01 00:00:00
abstract:OBJECTIVE:To examine whether oncogenic Ras affects transforming growth factor (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream signal transduction pathway involved in the interference with TGF-beta-induced cell-cycle arrest. MATERIALS AND METHODS:Two leukemic cell lines bearing N-Ras(L61...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.04.006
更新日期:2005-07-01 00:00:00
abstract:OBJECTIVE:The present study was designed to compare directly the frequency of circulating LTC-IC and E-LTC-IC mobilized in peripheral blood (PB) after chemotherapy supported by either G-CSF (PB-G) or GM-CSF (PB-GM) in comparison to steady-state bone marrow (BM) and PB (PB-ST) values in the same patients. MATERIALS AND...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00762-7
更新日期:2002-01-01 00:00:00
abstract::An unusual case of graft failure following bone marrow transplantation for aplastic anemia is reported in which the patient had delayed and incomplete recovery of hematopoiesis despite documentation of sustained engraftment. The pathophysiology of graft failure following bone marrow transplantation is discussed and re...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Previous studies have suggested that in vivo granulocyte colony-stimulating factor (G-CSF) pharmacokinetics may change over time. We studied three patients treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) for metastatic breast cancer after intravenous administration of reco...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:We have recently reported that 20% O2 significantly enhances total megakaryocyte (Mk) number, polyploidy, and proplatelet formation compared to 5% O2 in culture. In order to further elucidate the regulatory role of pO2 on megakaryocytopoiesis, we conducted a kinetic study of the expression of surface markers ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00658-0
更新日期:2001-07-01 00:00:00
abstract::The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morpholo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::This report presents the results of studies using long-term bone marrow cultures (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers established from human bone marrow cells were irradiated to eliminate residual hematopoietic progenitor cells a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Mouse bone marrow cells were cultured to determine some basic characteristics of the diffusion chamber (DC) technique. The main findings were as follows: (i) Incorporated 3H-thymidine was conveniently measured after deposition of a cell sample on glass fibre discs followed by methanol washing. Varying the specific act...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::We analyzed the accessory function of malignant B cells from non-Hodgkin's lymphomas (NHLs). Among the 70 samples of malignant B cells included, four patterns of expression of the costimulatory molecules CD80 and CD86 were distinguished (+/+, +/-, -/+ and -/-). In two-thirds of the cases, CD80, CD86, or both were expr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00059-9
更新日期:1999-03-01 00:00:00
abstract::Recent experimental data suggest that the heterogeneity of chronic myeloid leukemia (CML) stem cells may be the result of the development of unique molecular events generating functional consequences in terms of the resistance and persistence of leukemic stem cells. To explore this phenomenon, we designed a single-cel...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2020.04.005
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:The hematopoietic system is nurtured by a supportive stroma environment allowing maintenance and differentiation of hematopoietic stem cells (HSC). However, only a limited number of these stromal cell clones support hematopoiesis in the absence of cytokine supplementation. So far, only two bone marrow-derived...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.06.013
更新日期:2006-11-01 00:00:00
abstract::Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Expression of the main nuclear protooncogenes during terminal megakaryocyte (MK) differentiation is poorly understood. Because previous results have suggested that c-fos and c-jun protooncogenes are expressed in human leukemic cell lines induced to undergo megakaryocytic differentiation, we have analyzed the expressio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to evaluate the repopulating properties of bone marrow (BM) from mice irradiated during embryonic and adult stages of development. MATERIALS AND METHODS:Four-day-old embryos, 17-day-old fetuses, and 12-week-old mice were irradiated with of 1 or 3 Gy of x-rays. At 3 and 9 months ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00128-9
更新日期:2000-01-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by defects in the DNA damage response and apoptosis. Among the factors involved in these pathways, we focused on the enzyme poly(ADP-ribose) polymerase 1 (PARP1) and on its substrate Che-1 by evaluating their basal expression and functional ch...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2011.11.005
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVE:We previously showed enhanced engraftment of human T cells in the transgenic NonObese Diabetic/severe combined immunodeficient (NOD/scid)-DR1 mice, compared to NOD/scid mice. We now characterize their immunobiology, innate immunity, and intrahepatic neonatal engraftment of cord blood mononuclear cells (CBMNC)...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.05.002
更新日期:2007-08-01 00:00:00
abstract::Bone marrow stem cells reside in close proximity to endosteal osteoblasts. To explore the potential role of osteoblasts in hematopoietic differentiation, we measured the mRNA accumulation, protein production, and secretion of hematopoietic growth factors by the nonmineralizing MG-63 and the mineralizing SaOS-2 human o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-03-01 00:00:00
abstract::Between 30 and 40% of the CSF present in agar was depleted after culture for 1 week with 50,000 nucleated murine bone marrow cells. No statistically significant difference could be detected between this depletion and the extent of depletion of CSF when the amount present was halved. There was no evidence that toxic or...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found ins...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.010
更新日期:2016-05-01 00:00:00