Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selection of CD34+ hematopoietic progenitor cells from autografts may be performed in multiple myeloma (MM) to minimize contamination with tumor cells. This approach is based on the assumption that the malignant cells do not express the CD34 antigen. Therefore, we first compared the CD34+/CD10+ and CD34+/CD19+ subpopulations from bone marrow (BM) and peripheral blood (PB) of fourteen MM patients and five normal controls. No difference between the respective early B cell subsets of both groups could be observed. Using tricolor flow cytometry, the CD19 expression on CD34+/CD10+ cells in BM was found to increase continuously from CD19- to CD19dim. In contrast, circulating CD34+/CD10+ cells did not coexpress the CD19 antigen. This population may contain myeloid progenitor cells or bipotential progenitor cells of the myeloid and lymphoid lineage as suggested by data obtained with fetal liver cells. Further functional studies are required. Enrichment of CD34+ cells with immunomagnetic beads was performed from BM of three MM patients and four normal donors. The CD34+ cells were selected with the HPCA-1 antibody and detached from the beads with chymopapain. Compared with the starting cell preparation, a 3.97 +/- 0.48 log (mean +/- SE) reduction of plasma cells could be achieved after CD34 selection. On morphological examination, 84% +/- 4% of the cells in the CD34+ fraction (MM) were immature blasts. The plating efficiency for hematopoietic colony forming cells was 9.7% +/- 2.8% in the CD34 selected fraction of the MM group, reflecting a 51-fold increase as compared with the starting population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CD34 selection for purging in multiple myeloma and analysis of CD34+ B cell precursors. 751 57

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
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PMID:Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. 860 80

The CD34 antigen is a glycosilated transmembrane protein with a molecular weight of 105-120 kDs, whose molecular function is still unknown. At present different epitopes of this antigen are recognized by more than 20 monoclonal antibodies. By flow cytometry is quite simple to identify and enumerate the CD34+ cells, present in physiological conditions on 1-3% of normal bone marrow, 0,1-0,5% of cord blood and 0,001-0,01% of peripheral blood cells. The concomitant expression of other monoclonal antibodies allows the identification of different subsets, lineage negative or already lineage "committed", so that CD34+ cells represent an heterogeneous population with only a small number of undifferentiated progenitors. The number of circulating progenitors has highly increased in peripheral blood for few hours during the fast hematopoietic recovery after high dose chemotherapy. Growth factors are able to mobilize CD34+ cells if used alone in a short treatment schedule and the effect is amplified by combining growth factors with chemotherapy. With this treatment CD34+ cells can increase in peripheral blood up to 100-1000 fold the baseline concentration. Collection of large scale of peripheral stem cells is now possible using different models of continuous-flow blood cell separators. The vast majority of the cells harvested by apheresis are constituted by "committed" elements, myeloid peroxidase positive cells (40%), T lymphocytes (30%), monocytes (20%), B lymphocytes (1-2%), the CD34+ representing not more than 3-4% of the total cells collected. The main biological characteristic of the CD34+ cells is the capacity to reconstitute the myelo and lymphopoietic system after a myeloablative treatment. For this reason in the last few years there has been an increasing interest in using these particular stem cells in many clinical settings. Peripheral blood autografting is widely used in a large number of trials for the treatment of chemosensitive tumors. At present peripheral blood allogeneic transplants have been done in a number of patients sufficient to conclude that it is safe and able to give rise to a sustained marrow engraftment. Moreover, due to the fact that circulating stem cells are a mixture of indifferentiated progenitors and "committed" cells, the hematopoietic recovery is significantly faster both in autologous and allogeneic transplant setting. The increasing use of peripheral blood stem cells for autografting has raised the problem of tumoral contamination. The role of reinfused tumoral cells in promoting the relapse had been proved in the past. Attempts to "purge" the bone marrow of patients affected by low-grade non-Hodgkin lymphoma were done several years ago at Dana Farber Institute, strongly suggesting the importance of tumor cells left in the inoculum in modifying the prognosis. In certain tumors, such as myeloma for example, using a PCR based method, the contamination was found in all the aphereses tested. Similar data were found in samples derived from advanced breast cancer or small-cell lung cancer patients. These findings have brought to the development of different systems of stem cell "purging" or CD34+ positive selection. At present at least two or three different methods are available on the market for small and large scale bone marrow or peripheral blood stem cell processing. The ongoing trials will clarify the clinical utility. In the end the availability of large amount of enriched CD34+ cells have suggested to several investigators a possible target for gene therapy. The first data seem to suggest this is a good way to pursue, even if a clinical application remains still far from being satisfying.
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PMID:[CD34+ cells: biological aspects]. 892 36

Monoclonal plasma cells (CD38+CD45-/dim) are typically present in the blood of patients with active myeloma and can contaminate stem cell harvests. This has led to strategies that select CD34+ cells for use in autologous stem cell transplantation with the goal of decreasing tumor cell contamination. The aim of this study was to learn if the CD34 antigen is expressed on monoclonal plasma cells in the blood or marrow of patients with multiple myeloma. We used three-color flow cytometry (surface CD38;CD45 and cytoplasmic kappa or lambda) to identify monoclonal plasma cells in the blood (n = 24) and marrow (n = 37) from patients with plasma cell proliferative disorders. In each case the CD38+CD45- and CD38+CD45dim+ monoclonal populations were then analyzed for CD34 expression. In all 24 blood and 37 marrow samples, the CD38+CD45-monoclonal plasma cells were negative for CD34 expression. CD38+CD45dim+ monoclonal cells were documented in the blood of 11 patients and in the marrow of 33 patients and this cell population was also CD34-negative in all cases. These results indicate that CD34 is usually not expressed on the CD38+CD45-CD45dim+ monoclonal plasma cells in the blood or marrow of patients with plasma cell proliferative disorders. CD34 selection methods should therefore decrease the chance of tumor cell contamination of the stem cell product.
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PMID:Expression of the hematopoietic stem cell antigen CD34 on blood and bone marrow monoclonal plasma cells from patients with multiple myeloma. 908 34

The development of monoclonal antibodies against differentiation antigens on human haematopoietic cells has led to a new concept in stem cell purification: the positive selection. In terms of autologous PBSC transplantation, the immature stem cells are identified by their expression of a specific antigen, the CD34. The CD34 antigen is expressed on early lymphohaematopoietic stem cells and progenitor cells, but not on mature blood cells or on tumour cells of several diseases. CD34+ cells are found in low numbers in bone marrow (<2%) and in even lower numbers in steady state blood (<0.01%) but may increase from 1 to 5% after mobilization using chemotherapy and/or growth factors. Several techniques have been set up to enrich PBSC grafts in CD34+ stem cells. The quality of each system is here analysed in terms of CD34 purity of the selected cell fraction, the CD34 cell recovery, the tumour cell depletion efficiency and the functional capacity ex vivo and in vivo of the selected cells. The final CD34+ cell purity of the selected fractions is correlated to the concentration of CD34+ cells before selection. The optimal recoveries and the highest purities were generally obtained when the initial CD34 content was roughly over 1%. Below this figure, the final purity seems to be less predictable. Besides the better tolerance resulting from the reduction in the number of autologous cells, and consequently the total volume of DMSO reinfused to the patient, the selective enrichment of the CD34 cell population offers a new approach to tumour purging. The procedure by itself results in elimination of about 99% in the total number of initial cells, thus allowing reduction of the overall tumour cell number in the final autograft. However, its major interest is that, in diseases where tumour cells do not express the CD34 antigen, it is theoretically able to completely eliminate the tumour contamination of the graft. Based on previous data showing that lymphoma, myeloma, neuroblastoma and breast cancer cells are not CD34+, pilot clinical trials for the separation and transplantation of CD34+ cells selected from PBSC of patients with these diseases have recently been conducted. The efficacy of CD34 selection in reducing the tumour load of the PBSC of patients with these diseases has been reported. However, the efficacy of purging may greatly differ between individual patients, and complete eradication of contaminating cells from PBSC grafts was not always reached. There is now evidence that purified CD34+ cells are capable of supporting haematopoietic reconstitution in autologous transplantation. However, until now no study has demonstrated clear evidence that the reduction of tumour cells from PBSC of patients by CD34+ cell selection resulted in a lower relapse rate post-transplant, as compared to unselected PBSC infusion.
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PMID:Positive selection of autologous peripheral blood stem cells. 1100 Sep 84

New advances in apheresis technology allow for the safe and efficient collection of peripheral progenitor cells (PPC). Two blood cell separators were compared with respect to separation results such as PPC yield and contamination of the products. A total of 11 patients (6 multiple myeloma, 4 non-Hodgkin lymphoma, and 1 medulloblastoma) underwent PPC collections with either the Amicus (Baxter) or AS. TEC (Fresenius) blood cell separator. PPC were mobilized by chemotherapy and granulocyte colony-stimulating factor (G-CSF) application. Blood counts were determined before and after apheresis as well as in the PPC product. CD34 antigen-expressing cells were measured in the peripheral blood and in the PPC product by flow cytometry. Median baseline CD34 antigen-expressing cells were higher in patients undergoing PPC collection with the Amicus device. More PPC/kg of body weight were collected with this machine (5.3 x 10(6)/kg body weight versus 1.7 x 10(6) in the AS. TEC). The median volume was 129 ml (range 80-156 ml) for Amicus products and 111 ml (range 66-202 ml) for the AS. TEC, respectively. The median platelet contamination of the products from the Amicus blood cell separator was significantly lower than in products from the AS. TEC machine (0.17 x 10(11) versus 0.65 x 10(11), p < 0.001). The data show that a higher yield of PPC was collected with the Amicus machine. The platelet contamination of the products obtained from the two blood cells separators was significantly different.
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PMID:Comparison of two continuous-flow systems for the collection of peripheral progenitor cells. 1534 29

Telomerase activity has been found in most common cancers, thus indicating that telomerase detection may be a useful marker in cancer diagnosis. The telomeric amplification protocol (TRAP) assay and RT-PCR are customarily used to detect telomerase activity and the expression of the associated genes in cells. However, these methods do not provide any information about telomerase activation at an individual cell level. To analyze cells separately, those cells have to be isolated by sometimes complicated method. The immunohistochemical detection of human telomerase reverse transcriptase (hTERT) is useful to detect telomerase positive cells in a background of non-cancerous cells. A method has been developed for the detection of intranuclear hTERT protein, in a subpopulation of hematopoietic cells, using concurrent staining of a cell surface antigen and multicolor flow cytometry. Only mouse monoclonal anti-hTERT antibody demonstrated the specific positivity in immunocytochemistry and immunofluorescent flow cytometry. Human leukemia and myeloma cell lines showed 100% positivity, whereas normal neutrophils showed 0% positivity. hTERT expression was analyzed in hematopoietic precursor cells of bone marrow samples using concurrent staining of surface CD34 antigen and intracellular hTERT protein and multi-parameter flow cytometry. CD34 positive cells demonstrated higher expression of hTERT than CD34 negative cells. A quick, easy and sensitive assay for determining the hTERT protein expression has been developed. Using this method and the multi-parameter nature of flow cytometry and its ability to identify cellular subpopulations will provide a better understanding of the mechanisms regarding the activation of telomerase.
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PMID:Flow cytometric detection of human telomerase reverse transcriptase (hTERT) expression in a subpopulation of bone marrow cells. 1960 79