共查询到20条相似文献,搜索用时 15 毫秒
1.
R. F. Schlenk H. Döhner M. Pförsich A. Benner K. Fischer F. Hartmann J. Th. Fischer W. Weber U. Gunzer H. Pralle & R. Haas 《British journal of haematology》1997,99(2):386-393
We evaluated the feasibility of collecting peripheral blood progenitor cells (PBPC) in patients with acute myeloid leukaemia (AML) following two cycles of induction chemotherapy with idarubicin, cytarabine and etoposide (ICE), and one cycle of consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). Thirty-six patients of the multicentre treatment trial AML HD93 were enrolled in this study, and a sufficient number of PBPC was harvested in 30 (83%). Individual peak concentrations of CD34+ cells in the blood varied (range 13.1–291.5/μl; median 20.0/μl). To reach the target quantity of 2.5 × 106 CD34+ cells/kg, between one and six (median two) leukaphereses (LP) were performed. The LP products contained between 0.2 × 106 and 18.9 × 106 CD34+cells/kg (median 1.2 × 106/kg). Multivariate analysis showed that the white blood cell count prior to HAM and the time interval from the start of HAM therapy to reach an unsupported platelet count > 20 × 109/l were predictive for the peak value of CD34+ cells in the blood during the G-CSF stimulated haematological recovery. In 16 patients an intraindividual comparison was made between bone marrow (BM) and PBPC grafts. Compared to BM grafts, PBPC grafts contained 14-fold more MNC, 5-fold more CD34+ cells and 36-fold more CFU-GM. A CD34+ subset analysis showed that blood-derived CD34+ cells had a more immature phenotype as indicated by a lower mean fluorescence intensity for HLA-DR and CD38. In addition, the proportion of CD34+/Thy-1+ cells tended to be greater in the PBPC grafts. The data indicate that sufficient PBPC can be collected in the majority of patients with AML following intensive double induction and first consolidation therapy with high-dose cytarabine and mitoxantrone. 相似文献
2.
Using a sensitive fluorescent-polymerase chain reaction technique we looked for microsatellite instability (MSI) as functional evidence of mismatch repair defects in 71 cases of acute myeloblastic leukaemia (AML). MSI was assessed at 11 loci in matched leukaemic and constitutional DNA. Nine out of 71 patients (13%) were found to have MSI. Four of these patients had therapy-related leukaemia and the remaining five were all over the age of 60 years. There was a high incidence of adverse-risk cytogenetics in the patients with MSI, including abnormalities of chromosomes 5 and/or 7. Of the nine cases of t-AML included in this study, four (44%) had MSI. MSI was also seen in five of 51 cases (10%) over the age of 60 years but not in any cases under the age of 60 years with de novo AML. Using a sensitive assay, our results suggest that MSI occurs in two subgroups of patients with AML: those with t-AML and the elderly (> 60 years), but is rare in younger patients. 相似文献
3.
Marie Michèle DAUTEL Sylvie FRANÇOIS Marie-FranÇoise BERTHEAS Laurence BARANGER Jacques GARDAIS Marc BOASSON Norbert IFRAH & Odile BLANCHET 《British journal of haematology》1997,98(1):210-212
We report a case of chronic myelomonocytic leukaemia (CMML), which transformed first into acute myeloblastic leukaemia (AML) and then into acute lymphoblastic leukaemia (ALL). In the AML and ALL phases, chromosome analysis showed a classic Philadelphia chromosome (Ph) t(9;22)(q34;q11). Molecular studies showed breakpoint cluster region rearrangement between exons e1 and a2 compatible with a p190bcr/abl breakpoint as observed in Ph-positive lymphoblastic acute leukaemia. The minor (m-bcr) rearrangement was also detected during complete remission.
This observation supports a multistep pathogenesis of leukaemias, and that the p190bcr/abl breakpoint may influence the course of the disease. 相似文献
This observation supports a multistep pathogenesis of leukaemias, and that the p190
4.
Neoplastic circulating endothelial-like cells in patients with acute myeloid leukaemia 总被引:1,自引:0,他引:1
Rigolin GM Mauro E Ciccone M Fraulini C Sofritti O Castoldi G Cuneo A 《European journal of haematology》2007,78(5):365-373
Accumulating evidence suggests that angiogenesis may play a key role in the pathogenesis of leukaemic disorders. Several studies have shown that bone marrow-derived endothelial cells (EC) may contribute to tumour angiogenesis and that in the peripheral blood of cancer patients there is an increased amount of circulating ECs (CECs) that may participate to new vessel formation. In this report, we showed that, in seven acute myeloid leukaemia (AML) patients with known cytogenetic abnormalities, CEC levels were significantly increased in comparison with controls and that a significant proportion of these CECs carried the same chromosomal aberration as blast cells (20-78%, mean value 42.1% of CECs). Most of CECs (mean value 74.4%) displayed immunophenotypic features of endothelial progenitor cells as they expressed CD133, a marker gradually lost during EC differentiation and absent on mature EC. These findings suggest a possible direct contribution of AML-related CECs to tumour vasculogenesis and possibly to the spreading and progression of the disease. 相似文献
5.
Summary From 17 patients with different forms of acute leukaemia, mononuclear blood cells were cultured in diffusion chambers (DC) implanted intraperitoneally into pre-irradiated mice. In 14 patients, growth of blast cells could be observed during the culture period of up to 21 days. To question whether this growth of blast cells was due only to proliferation of the initially proliferating fraction or whether a re-entry of resting leukaemic cells into proliferation was involved, various3H-thymidine (3H-TdR) labelling studies were carried out. The absolute increase of blast cells in DC showed no correlation with the fraction of leukaemic blast cells in DNA-synthesis in the implanted cell suspension as measured by3H-TdR labelling in vitro. Further-more, in 2 patients where the kinetic behaviour of initially labelled leukaemic blast cells was followed during DC culture, the increase in total blast cells could only be attributed to a small extent to proliferation of those cells initially in the cell cycle. Lastly, in vivo labelling during the culture period showed that in one case 25% and in another case 60% of the blast cells in DC were proliferating. The conclusion is that, owing to the stimulation of the diffusion chamber milieu and possibly also due to removal of an in vivo inhibition, in most cases of acute leukaemia resting leukaemic blast cells can apparently re-enter the active cell cycle. This has relevance for an understanding of the self-maintenance of the leukaemic cell population and may also be a reason for relapse of leukaemia after the usual cytostatic drug treatment which affects mainly the proliferating leukaemic cells.
Zusammenfassung Von 17 Patienten mit verschiedenen Formen der akuten Leukämie wurden mononukleäre Blutzellen in Diffusionskammern, welche intraperitoneal in vorbestrahlte Mäuse implantiert wurden, kultiviert. Bei 14 Patienten fand sich ein Wachstum von Blasten während der Kulturperiode. Zur Frage, ob dieses Blastenwachstum allein durch Teilung der zu Beginn in Proliferation befindlichen Zellpopulation erklärt werden kann oder ob zusätzlich ein Wiedereintritt leukämischer Zellen in Proliferation postuliert werden muß, wurden verschiedene3H-Thymidinuntersuchungen durchgeführt. Es zeigte sich, daß keine Korrelation zwischen absoluter Zunahme der Blasten und Anzahl der implantierten leukämischen Zellen in DNA-Synthese, gemessen am3H-Thymidinmarkierungsindex des peripheren Blutes, bestand. Bei 2 Patienten, bei denen3H-Thymidin-markierte Zellen in Diffusionskammern implantiert wurden, konnte der Blastenanstieg nur teilweise durch eine Proliferation dieser Zellen erklärt werden. Außerdem stieg der in vivo-3HTdR-Markierungsindex der Blasten während der Diffusionskammerkultur bei 2 weiteren Patienten auf 25 bzw. 60% an. Auf Grund dieser Befunde muß man annehmen, daß durch die Stimulationsbedingungen der Diffusionskammer, möglicherweise zusätzlich durch den Wegfall einer in vivo wirksamen Inhibition, ruhende Leukämiezellen wieder aktiv in Proliferation eintreten. Dieser Befund ist nicht nur relevant für das Verständnis der Leukämiezellvermehrung, sondern könnte auch erklären, warum es nach einer Chemotherapie, die hauptsächlich proliferierende Zellen zerstört, zu einem Rezidiv kommt. Andererseits werden therapeutische strategische Konzepte bei der akuten Leukämie, die auf einem Wiedereintritt leukämischer Ruhezellen in Proliferation basieren, theoretisch unterstützt.相似文献
6.
7.
目的探讨从正常人经粒细胞集落刺激因子(granulocyte colony simulating factor,G-CSF)动员的外周血中分离扩增内皮祖细胞(endothelial progenitor cells,EPCs)。方法经G-CSF动员后,富集的外周血单个核细胞(peripheralblood mononuclear cells,PBMNC)贴壁培养法定向扩增EPCs,免疫组织化学染色和荧光标记鉴定其内皮细胞特性。流式细胞仪检测细胞表面标记物变化。结果获得的贴壁细胞数为(8.825±2.958)个/100个PBMNC,具有多种内皮细胞特征,血管性假血友病因子阳性,同时结合荆豆凝集素I并内吞乙酰化低密度脂蛋白呈红绿荧光双染色。培养后血细胞标记物减少,内皮细胞标记物增加(P<0.01)。结论从G-CSF动员的外周血中可获得较多数量EPCs,并具有多种内皮细胞特征。 相似文献
8.
Cario G Skokowa J Wang Z Bucan V Zeidler C Stanulla M Schrappe M Welte K 《British journal of haematology》2005,129(2):275-278
Apoptosis is accelerated in the myeloid progenitor cells of patients with severe congenital neutropenia (CN). Granulocyte colony-stimulating factor (G-CSF) increases neutrophil numbers in most CN patients. The effect of G-CSF on apoptosis in CN was analysed by apoptosis rate and expression of anti- and pro-apoptotic factors. G-CSF-treated patients showed higher apoptosis frequency, lower expression of bcl-2 and bcl-xL, but higher expression of bfl-1/A1 and mcl-1. Caspase 9 was highly expressed in patients and controls after G-CSF administration. Thus, G-CSF acts on apoptosis regulation, but additional mechanisms leading to the increase of neutrophil numbers must be assumed. 相似文献
9.
George Katrinakis Despina Kyriakou Michael Alexandrakis Dimitra Sakellariou Andreas Foudoulakis George D. Eliopoulos 《European journal of haematology》1995,55(1):33-41
Abstract: B-cell chronic lymphocytic leukaemia (B-CLL) is often associated with peripheral blood cytopenias resulting, in most cases, from bone marrow infiltration, hypersplenism, or circulating autoantibodies. The present study was undertaken to investigate the possible involvement of a cell-mediated suppression of granulopoiesis in these patients. We studied two groups of patients, 8 neutropenic and 26 non-neutropenic, defined by the arbitrarily taken cutoff count of 2000 neutrophils/μl. We found that neutropenic patients had higher numbers of peripheral blood CD3 +, CD8 +and CD57+cells, and higher numbers of activated CD8 +/HLA-DR +cells than the non-neutropenic ones. A negative correlation between CD8 +cells and circulating neutrophils, and a suggested negative correlation between CD8 +/HLA-DR+cells and circulating neutrophils were noted in the patients studied. Furthermore, we investigated the capacity of immunomagnetically isolated CD8 +cells to inhibit in vitro colony formation by normal granulocyte/macrophage colony-forming units (CFU-GM) and we found that inhibition was more pronounced when CD8 +cells, added in the culture, were derived from neutropenic than from non-neutropenic patients. The degree of colony inhibition correlated with the number of circulating neutrophils and the numbers of CD8+and CD8 +/HLA-DR +cells in the patients studied. Since tumour necrosis factor-α (TNF-α) has been reported to be involved in myelosuppression, we also investigated the capacity of isolated CD8+cells to release this cytokine into the culture supernatant fluids, and we found that comparable amounts of TNF-α were produced after stimulation in both neutropenic and non-neutropenic patients. Elevated serum TNF-α concentrations were noted only in a number of neutropenic and non-neutropenic patients. All these data taken together provide strong evidence that a T-cell subpopulation of activated CD8 +/HLA-DR+cells may be involved in the pathogenesis of neutropenia, at least in a subset of B-CLL patients, suppressing myelopoiesis by a TNF-α-unrelated mechanism. Efforts to isolate this cell subpopulation by flow cytometry for further analysis and a better understanding of its effect on myelopoiesis in patients with B-CLL are in progress in our laboratory. 相似文献
10.
Akihiro Takeshita Kaori Shinjo Masakazu Izumi Pan Ling Satoki Nakamura Kensuke Naito Kazunori Ohnishi & Ryuzo Ohno 《British journal of haematology》1998,100(2):283-290
Using a non-isotopic ligand binding assay, we quantitatively examined the amount of human thrombopoietin (TPO) receptor (TPO-R) on leukaemia cells from 128 patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). The TPO-R was expressed in 53 (47%) of 114 AML cases, and an in vitro treatment with TPO led to proliferation (stimulation index >1.5) of leukaemia cells in 13 (20%) of 66 AML cases examined. The TPO levels had no relation to the FAB classification except for FAB-M7 AML. All five FAB-M7 cases expressed TPO-R, and one of three FAB-M7 examined showed in vitro proliferative response to TPO. Although there was no significant correlation ( r = 0.3125) between the amount of TPO-R and the proliferative response, all of the AML cases which showed the in vitro response had TPO-R expression. There was no relationship between TPO-R amount and CD phenotypes, or the amount of granulocyte-colony stimulating factor (G-CSF) receptor. TPO-R was also expressed in two (14%) of 14 cases of ALL, and only these two cases had in vitro proliferative response to TPO. One had only lymphoid antigens, and the other had both lymphoid and myeloid antigens. Our results suggest that some leukaemia cells express functionally active TPO-R. 相似文献
11.
Anna Carter Nuhad Haddad Ilana Draxler Ella Israeli Batya Raz Jacob M. Rowe 《British journal of haematology》1996,92(1):116-126
Tumour necrosis factor (TNF)-α exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-α-driven growth regulation of AML blasts in vitro. Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-α-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-α-induced autocrine growth. In contrast, the TNF-α-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-α on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-α-signalled growth inhibition is exclusively transduced via TNF-Rp55. 相似文献
12.
Abstract: To further characterise the regulation of haematopoiesis in hairy-cell leukaemia (HCL), we investigated the effect of mononuclear cells from peripheral blood (PBMNC) of untreated HCL patients on the in vitro growth of BFU-e. The effect was tested in an autologous system employing post-treatment HCL PBMNC, and in an allogeneic system. A significant enhancing effect of the pre-treatment HCL PBMNC was seen. In contrast to studies by others, IFN-α consistently inhibited the growth of BFU-e from normal donors, from pre- and post-treatment HCL PBMNC, and mixtures thereof. Since PBMNC from patients with very high percentages of circulating hairy cells (HC) also had an enhancing effect, HC was a likely source of one or more enhancing factors. Thus, even though we cannot exclude a minor inhibitory activity of the HC by our assay, their net effect seems to be enhancing, and therefore it seems unlikely that the HC is directly responsible for the anaemia in HCL. 相似文献
13.
Otten J Schultze A Schafhausen P Otterstetter S Dierlamm J Bokemeyer C Brummendorf TH Fiedler W Loges S 《British journal of haematology》2008,142(1):115-118
The existence of adult haemangioblasts with dual haematopoietic and endothelial developmental potential was confirmed after detection of Ph+ vascular endothelial cells in chronic myeloid leukaemia (CML) patients. Blood outgrowth endothelial cells (OECs) from CML patients were found not to harbour the Philadelphia translocation and were thus not clonally related to BRC/ABL1 + hematopoietic progenitors, but comprised a distinct subfraction of endothelial cells. Remarkably, the frequency of CML-derived OECs was 9-fold higher as compared to healthy donors ( n = 19 and n = 300, respectively; P < 0·0001) and these cells showed increased proliferative potential, possibly reflecting the mobilisation of OEC progenitors by pro-angiogenic cytokines. 相似文献
14.
Mäntymaa P Siitonen T Guttorm T Säily M Kinnula V Savolainen ER Koistinen P 《British journal of haematology》2000,108(3):574-581
We investigated the possible roles of mitochondrial manganese superoxide dismutase (MnSOD) and bcl-2 in etoposide-induced cell death in acute myeloblastic leukaemia (AML) using two subclones of the OCI/AML-2 cell line, the etoposide-sensitive (ES) and the etoposide-resistant (ER), as models. Cell death after 24 h exposure to 10 micromol/l etoposide was about 60% and 70% in the ES subclone and about 20% and 25% in the ER subclone, when analysed by trypan blue and annexin V respectively. Cytochrome c efflux from mitochondria to cytosol was observed after 4 h of exposure in both subclones, whereas the activation of caspase-3 was not detectable until after 12 h of exposure in the ES subclone and 24 h of exposure in the ER subclone, using Western blotting. The decrease in mitochondrial membrane potential, when analysed by the JC-1 probe fluorocytometrically, also appeared to take place later in the ER than in the ES subclone. Both subclones showed evident basal expression of MnSOD and bcl-2 by Western blotting. Etoposide caused a potent induction of MnSOD, more than 400% at 12 h, in the ER but not in the ES subclone. No significant change in bcl-2 expression could be observed in either of the subclones during exposure to etoposide when analysed by Western blotting or flow cytometry. In conclusion, we suggest that MnSOD might have a special role in the protection of AML cells against etoposide-induced cell death. Although unable to influence the cytochrome c efflux to cytosol, MnSOD might prevent the disruption of mitochondrial membrane potential, which evidently leads to cell death by releasing various activators of apoptosis. 相似文献
15.
E. Trnebohm D. Lockner C. Paul N. Egberg H. Sablica R. Wallin 《European journal of haematology》1992,49(2):98-104
Proteolysis of coagulation factors and inhibitors resulting in haemorrhage can be mediated by elastase. Indirect signs of this are elevated levels of elastase complexed to its inhibitor in plasma, alpha 1-antitrypsin (E alpha 1-AT). We have measured intracellular elastase activity in leukaemic cells from 60 patients with acute leukaemia. Elastase activity was detected in 92% of the patients with acute nonlymphoblastic leukaemia (ANL), no activity was found in the patients with acute lymphoblastic leukaemia (ALL). High levels were found in cells from patients with promyelocytic leukaemia. Moderate to high total circulating blast elastase activity was measured in 70% of the ANL patients with haemorrhage compared with 36% of the patients without bleeding complications (p < 0.05). The available intracellular elastase activity was correlated to the level of E alpha 1-AT (rs = 0.42, p < 0.01) but not to the elastase specific split product of fibrinogen, B beta 30-43. In complete remission the levels of E alpha 1-AT were normalized. Intracellular elastase activity might be a useful supplement to differentiate ANL and ALL. 相似文献
16.
Anna Carter Nuhad Haddad Ilana Draxler Ella Israeli Batya Raz & Jacob M. Rowe 《British journal of haematology》1995,92(1):116-126
Tumour necrosis factor (TNF)-α exerts multiple effects on human acute myeloblastic leukaemia (AML) cells in vitro , including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF); (2) inhibition of granulocyte-CSF (G-CSF) and stem cell factor (SCF)-induced growth; (3) suppression of multiplication of clonogenic leukaemic cells; (4) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-Rp55 and TNF-Rp75, have been identified. In this study we show that both receptors are expressed on freshly isolated AML blasts, with p75 being the predominant TNF-receptor type. This study investigates the roles of these two receptors in TNF-α-driven growth regulation of AML blasts in vitro . Using a receptor-specific antibody, it is shown that both receptor types participate in TNF-α-mediated stimulation of GM-CSF/IL-3-induced proliferation and in TNF-α-induced autocrine growth. In contrast, the TNF-α-triggered growth inhibition (antiproliferation) and the potent suppression of G-CSF- and SCF-induced proliferation exclusively result from activation of TNF-Rp55. Taken together, these results suggest that the proliferative effects of TNF-α on AML blasts are mediated through both p55 and p75 TNF receptors, whereas the TNF-α-signalled growth inhibition is exclusively transduced via TNF-Rp55. 相似文献
17.
Del Caizo Brufau Almeida Galende GarcÍa Marcos Mota GarcÍa Fernndez Calvo Ramos Fisac Orfao San Miguel 《British journal of haematology》1998,103(1):137-142
The in vitro growth characteristics of a large series of acute myeloid leukaemia (AML) patients and their relationship with other clinical and biological disease characteristics were analysed. Patients with AML were studied, 181 with de novo AML and 45 with secondary AML (24 myelodysplastic syndrome, sAML-MDS, 21 myeloproliferative disorder, sAML-MPD). Leukaemic colony forming units (L-CFU) were assayed by plating peripheral blood (PB) blast cells in methyl-cellulose and using LCM-PHA as stimulant. In each case parallel cultures were made with and without stimulating factors. Plating efficiency (PE) was defined as the number of clusters plus colonies/105 cells plated. Autonomous growth (AG) was the number of colonies plus clusters growing without stimulant. The autonomous proliferative index (API) was calculated as the number of clusters + colonies without stimulating factor divided by the number of clusters + colonies with stimulating factor. No significant differences in the PE between de novo and secondary AML were found. Autonomous growth was significantly higher in sAML-MPD. The FAB subtype M3 leukaemias displayed a significantly greater PE and a significantly lower API when compared with the other FAB subgroups (P = 0.0002). Upon analysing the relationship with the immunophenotype, only CD33 expression showed a significant relationship with the in vitro growth pattern; CD33+ cases displayed a higher PE (P = 0.0002) and AG (P = 0.0003) than CD33? cases. When patients were grouped according to the level of rh123 efflux (MDR1) it was observed that cases with >30% elimination showed a higher AG and API than those with <30% (P = 0.03). Finally we found that patients with higher API (>0.05) displayed a significantly shorter overall survival as compared with patients with API < 0.05 (P = 0.04). The in vitro study properties of clonogenic cells produces relevant clinical information of leukaemic cell biology in AML patients. 相似文献
18.
Fischer JC Frick M Wassmuth R Platz A Punzel M Wernet P 《British journal of haematology》2005,130(5):740-746
Granulocyte colony-stimulating factor (G-CSF) effectively mobilises haematopoietic stem cells to the peripheral blood. It is unclear whether the mobilisation of stem cells with lenograstim (glycosylated G-CSF) or filgrastim (non-glycosylated G-CSF) leads to a higher cell number of collected engraft able progenitor cells. Thus, we investigated harvesting efficiency of the licensed G-CSF preparations in mobilising peripheral stem cells in a randomised study. A total of 501 healthy unrelated donors, including 339 males and 162 females received either lenograstim (n = 261) or filgrastim (n = 240) at 10 microg/kg body weight (BW) per day. Aphaeresis was performed on day 5 and, if necessary, on day 6 of mobilisation. The number of CD34+ cells collected was 11.5% higher in the lenograstim group (7.19 x 10(6) vs. 6.44 x 10(6)/kg BW donor; P < 0.03). Univariate variance analysis revealed that this effect was caused by male donors: more progenitors cells per kg BW of the donor (7.73 x 10(6) vs. 6.88 x 10(6); P < 0.017) and of the recipient (10.1 x 10(6) vs. 8.88 x 10(6), P < 0.029) could be harvested. There was no significant difference in the percentage of donors in whom a second aphaeresis was required (9.6% vs. 11.6%). Lenograstim mobilises progenitor cells into the peripheral blood more effectively in males than filgrastim. 相似文献
19.
Grassinger J Mueller G Hart C Nilsson SK Haylock DN Andreesen R Hennemann B 《European journal of haematology》2008,80(1):20-30
Objective: Hematopoietic progenitor cells (HPC) as well as tissue committed stem cells expressing mRNA specific to various somatic tissues are thought to be part of the CD34+ bone marrow compartment. In this study, we explore and quantify their mobilization in patients with multiple myeloma undergoing chemotherapy upon administration of granulocyte colony-stimulating factor (G-CSF) plus/minus erythropoietin (EPO).
Patients and methods: HPC were quantified by flow cytometry and functional assays within the blood of healthy donors and myeloma patients before and after chemotherapy followed by G-CSF or G-CSF + EPO given subcutaneously. The mRNA expression was studied by quantitative polymerase chain reaction (PCR). Cytokines and peripheral blood protease levels were measured by an enzyme-linked immunosorbent assay.
Results: EPO did not significantly alter the number of HPC mobilized by G-CSF alone, and mRNA specific for liver, brain, muscle and kidney was detected in both treatment groups. Quantitative PCR analysis revealed a 2.7-fold increased expression of glial fibrillary acidic protein after G-CSF + EPO administration compared to G-CSF alone ( P = 0.003). The concentration of G-CSF rose from 62 ± 22 pg/mL and 48 ± 10 pg/mL to 28 ± 9 ng/mL and 85 ± 10 ng/mL after 10 d of treatment with G-CSF and G-CSF + EPO, respectively. The concentration of neutrophil elastase (NE) rose only in the G-CSF group by a factor 1.5.
Conclusion: The alteration of G-CSF and NE levels as well as the expression of tissue committed RNA after the administration of EPO in addition to G-CSF indicate that different growth factors mobilize different stem cells that might potentially be used for the support of tissue repair in future treatment protocols. 相似文献
Patients and methods: HPC were quantified by flow cytometry and functional assays within the blood of healthy donors and myeloma patients before and after chemotherapy followed by G-CSF or G-CSF + EPO given subcutaneously. The mRNA expression was studied by quantitative polymerase chain reaction (PCR). Cytokines and peripheral blood protease levels were measured by an enzyme-linked immunosorbent assay.
Results: EPO did not significantly alter the number of HPC mobilized by G-CSF alone, and mRNA specific for liver, brain, muscle and kidney was detected in both treatment groups. Quantitative PCR analysis revealed a 2.7-fold increased expression of glial fibrillary acidic protein after G-CSF + EPO administration compared to G-CSF alone ( P = 0.003). The concentration of G-CSF rose from 62 ± 22 pg/mL and 48 ± 10 pg/mL to 28 ± 9 ng/mL and 85 ± 10 ng/mL after 10 d of treatment with G-CSF and G-CSF + EPO, respectively. The concentration of neutrophil elastase (NE) rose only in the G-CSF group by a factor 1.5.
Conclusion: The alteration of G-CSF and NE levels as well as the expression of tissue committed RNA after the administration of EPO in addition to G-CSF indicate that different growth factors mobilize different stem cells that might potentially be used for the support of tissue repair in future treatment protocols. 相似文献
20.
Prokopia T. Tatsidou Vasileios G. Chantzichristos Maria E. Tsoumani Sofia Sidiropoulou Ioannis V. Ntalas John A. Goudevenos 《Platelets》2019,30(3):314-321
CD34+ cells expressing KDR (CD34+/KDR+) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34+ and CD34+/KDR+ progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y12 receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34+ and CD34+/KDR+ progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34+ and CD34+/KDR+ cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34+ (CD61+/CD34+) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR+ (CD61+/KDR+) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34+ cells and the CD61+/KDR+ conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR+ conjugates and CD34+ cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration. 相似文献