Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte colony-stimulating factor (G-CSF) has strong leukopoietic activity and it is used for patients with leukopenia during leukemia chemotherapy. However, some leukemia cells show a high affinity to G-CSF and are driven to proliferative phase. In our laboratory, we developed two testing methods. 1) Flow cytometric method on G-CSF susceptibility of leukemia cells using FITC-labeled G-CSF, and 2) Immunohistochemical method for detecting the ratio of cells driven from dormant phase to proliferative phase by G-CSF with anti-PCNA antibody and Ki-67 antibody. In MDS patients G-CSF administration induced an increase of cells in proliferative phase. The patients treated with cytosine arabinoside following G-CSF showed hematologically good improvement. A new mode of therapy using G-CSF in combination with other cytokines or antileukemic agents will be developed in the near future for treatment of leukemia patients.
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PMID:[Recent trend in G-CSF therapy and clinical laboratory tests]. 128 10

We have investigated proliferation in bone marrow trephine biopsies from 32 patients with normal or abnormal haemopoiesis, using the monoclonal antibody PC10, which detects proliferating cell nuclear antigen (PCNA), together with immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining revealed the pattern of proliferation within individual haemopoietic lineages in normal marrow. Two unexpected observations were made: of erythroid cells, only pro-erythroblasts and occasional early normoblasts reacted, and positivity of megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The pathological cases represented conditions in which haemopoiesis is increased (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and disturbances of the spatial organization, of PCNA-expressing cells were present to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid erythrocytes were frequently found in myelodysplastic and myeloproliferative tissue, associated with marked disturbances in the spatial organization of all haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate deficiency also demonstrated greatly increased erythroid PCNA expression, with positivity in some giant metamyelocytes. In addition to reflecting increased proliferation, elevated PCNA expression in some bone marrow pathologies may be due to altered kinetics of the protein induced by disturbances in growth factor production.
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PMID:A study of cell proliferation in formalin-fixed, wax-embedded bone marrow trephine biopsies using the monoclonal antibody PC10, reactive with proliferating cell nuclear antigen (PCNA). 134 81

Histopathologic diagnosis of the bone marrow in leukemia is usually a supplementary method to the cytological in acute and chronic leukemia. However, for patients with MDS and MPD and with dry tap bone marrow biopsy is very important. Important morphological findings and useful immunohistochemical methods for differentiation and characterization of leukemia are reported and the usefulness of sequential examination of bone marrow in leukemia during and after chemotherapy is emphasized. In addition to leukemia, histological features and differential points of myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPD) are mentioned. The proliferating megakaryocytes differed in size and shape between MDS and MPD. The difference in proliferating rate of the cells examined by PCNA was also useful to differentiate the two disorders histologically.
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PMID:[Histopathologic diagnosis of bone marrow in leukemia and related disorders]. 177 61

There is general agreement on the fact that bone marrow macrophages present a non-proliferating cell population. Using a sequential double-immunostaining technique, a morphometric analysis was performed on routinely processed bone marrow biopsies derived from 70 patients. The purpose of this study was, firstly, to determine the frequency of bone marrow macrophages in a variety of lesions and, secondly, to elucidate whether there is any proliferative activity detectable by immunohistochemical markers. Bone marrow pathology included reactive myelitis (RM), secondary aplastic anaemia (AP), AIDS-related myelopathy, primary (idiopathic) osteomyelofibrosis (OMF) and myelodysplastic syndromes (MDS). The monoclonal antibody PG-M1 which recognizes a formalin-resistant epitope on macrophages and PC10 raised against proliferating cell nuclear antigen (PCNA) were employed. For comparison with the PCNA-labelling index, the newly developed monoclonal antibody Ki-S1, which is associated with cell proliferation, was applied. In comparison with normal bone marrow, morphometric evaluation revealed a significant increase in macrophages in MDS, OMF, RM and especially in HIV-infected patients. Moreover, a positive immunostaining of single macrophages with PC10 was noted very infrequently. This rather inconspicuous PCNA labelling increased in AIDS. By contrast, Ki-S1 expression was found in none of the other pathologies studied. The prevalence of the macrophage population in certain disorders may have a multifactorial origin, such as inflammatory changes like intercurrent infections in AIDS and enhanced cell turnover in MDS as well as involvement of the complex pathomechanisms generating bone marrow fibrosis. In keeping with previous studies, the insignificant PCNA expression of macrophages should not be related to cell proliferation, but to unscheduled DNA strand repair which may be generated in the course of viral infection in AIDS.
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PMID:Ki-S1 and proliferating cell nuclear antigen expression of bone marrow macrophages. Immunohistochemical and morphometric study including reactive (inflammatory) myelitis, secondary aplastic anemia, AIDS, myelodysplastic syndromes and primary (idiopathic) osteomyelofibrosis. 752 84

In this study we describe the morphologic and immunohistochemical evaluation of bone marrow biopsies from 14 patients with therapy-related myelodysplastic syndromes (t-MDS). We employed CD34, anti-HLA-Dr, anti-elastase, CD68, anti-glycophorin, CD61 monoclonal antibodies immunostaining, and enzyme histochemistry for chloroacetate esterase. Moreover, we used PC10, a MAb raised against the proliferating cell nuclear antigen, to study the proliferative capacity of these marrows. Our data suggest that diagnosis of refractory anemia with excess of blasts (versus chronic myelomonocytic leukemia), the abnormal localization of immature precursors, marrow fibrosis, and augmented CD34 expression in the bone marrow biopsy are ominous prognostic factors at a statistically significant level (p < 0.0005). A combined morpho-immunohistochemical analysis of bone marrow biopsy correctly classifies t-MDS cases according to the biologic and clinical aggressiveness.
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PMID:Therapy-related myelodysplastic syndromes: FAB classification, bone marrow histology, and immunohistology in the prognostic assessment. 768 97

To determine the proliferative activity of the hematopoietic cells under nonneoplastic and/or neoplastic conditions, the expression of a cell cycle-related antigen, the proliferating cell nuclear antigen (PCNA), was examined in the bone marrow trephines of 79 individuals, 12 of whom had no hematologic disorder, 32 of whom had a diagnosis of myelodysplastic syndromes (MDSs), 20 of whom suffered from aplastic anemia, and 15 of whom had a diagnosis of acute myeloid leukemia. Most of the patients with MDS had more than 15% PCNA-positive cells (23.5% +/- 1.5%) while patients with no hematologic disorder showed fewer than 15% PCNA-positive cells (11.7% +/- 0.7%). The overall ratio of the PCNA-positive cell fraction in the bone marrow was considered of prognostic value for predicting transition into overt leukemia from MDS. Aplastic anemia cases usually exhibited hypocellular bone marrow and an infrequent labeling with the anti-PCNA antibody (3.3% +/- 0.5%). However, a few aplastic anemia cases showed hypercellular bone marrow and a significantly high PCNA-positive cell ratio (32.0% +/- 4.4%). In the bone marrow of acute myeloid leukemia patients more than 20% of total nucleated cells were positive for PCNA (30.0% +/- 2.2%). The results suggest that the expression of PCNA is associated with the regulation of bone marrow cell proliferation and the bone marrow cellularity, and that these findings would serve as an early indicator of evolution of overt leukemia in MDS and also would be useful in distinguishing MDS cases from aplastic anemia cases when the bone marrow is hypocellular or normocellular.
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PMID:Expression of the proliferating cell nuclear antigen in bone marrow cells from patients with myelodysplastic syndromes and aplastic anemia. 809 17

An immunohistochemical and morphometric analysis was performed on bone marrow trephine biopsies in 40 patients with primary myelodysplastic syndromes (MDS) to evaluate the proliferative activity in erythropoiesis and the endoreduplicative capacity of megakaryocytes. Control groups included normal bone marrow and marrow from cases presenting with pernicious anaemia. Double-immunostaining was applied with a monoclonal antibody (PC10) directed against proliferating cell nuclear antigen (PCNA), followed by antibodies against glycophorin C (Ret40f) or platelet glycoprotein IIIa (Y2/51-CD61) for the identification of the erythroid and megakaryocytic cell lineage. Comparison with normal bone marrow showed a reduction of erythropoiesis accompanied by an increase in atypical (micro-) megakaryocytes. Erythroid precursors displayed significant enhancement of PCNA-immunostaining. Megakaryocytes showed no increase in the relative frequency of PC10-positive cells (PCNA-labelling index). In pernicious anaemia, predominance of macrocytic-megaloblastoid erythropoiesis was associated with a striking increase in PCNA-labelling. Cell kinetic studies in this disorder revealed an abnormal arrest, particularly in S-phase which generates an over-expression of PCNA. Similar conditions were believed to be present in MDS with secondary folate deficiency. This mechanism explains the relatively high rate of positively-reacting pro- and erythroblasts which is not invariably accompanied by an increase in cell proliferation. Determination of megakaryocyte size and PCNA-staining capacity resulted in a significant increase in PC10-positive cells among micromegakaryocytes. Our findings on this cell lineage are in keeping with the assumption of a block in endoreduplicative activity at higher ploidy levels, associated with an apparently not-deregulated endomitosis in small-sized megakaryocytes of lower ploidy stages.
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PMID:Myelodysplastic syndromes: immunohistochemical and morphometric evaluation of proliferative activity in erythropoiesis and endoreduplicative capacity of megakaryocytes. 810 4

There seems to be general agreement that AIDS-related bone marrow changes are consistent with myelodysplastic features. To re-evaluate this assumption more critically, a comparative study was performed on marrow smears and trephine biopsies in 20 patients presenting manifest stages of AIDS and in 30 patients with primary myelodysplastic syndromes (MDS). For an assessment of cytological atypias enzyme-(naphthol AS-D-chloroacetatesterase) and immuno-histochemical techniques including monoclonal antibodies directed against erythro-(Ret40f) and megakaryopoiesis (CD61), macrophages (PG-M1) and proliferating cell nuclear antigen-PCNA (PC10) were applied and staining results determined by morphometric analysis. The in situ end-labeling (ISEL) technique was used for the demonstration of cells undergoing apoptosis (programmed cell death). In the HIV-infected bone marrow the frequency of erythroid precursors and macrophages exceeded significantly the corresponding counts in MDS. In comparison with a control group, megakaryocytes were increased in both entities under study. However, MDS was characterized by a prevalence of atypical microforms. The small-sized megakaryocytes in MDS revealed striking abnormalities of nuclear-cytoplasmic organization. Severe defects of nuclear lobulation (pseudo-Pelger anomalies) of mature neutrophils or nuclear bridging of erythro-normoblasts were not conspicuous in AIDS. Whereas the incidence of apoptosis was significantly higher in MDS, no such differences could be found comparing the PCNA-labeling index of AIDS and MDS. On the other hand, both parameters were significantly increased in comparison with the controls. In the HIV-infected bone marrow alterations of the myeloid stroma were most prominently expressed. If well defined criteria for the diagnosis of (myelo-) dysplasia were applied, our findings in AIDS were not in keeping with the assumption of significant maturation defects comparable with MDS. Hence, bone marrow lessions accompanying AIDS should be separated from MDS and should be diagnosed as HIV-myelopathy.
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PMID:AIDS-related bone marrow lesions--myelodysplastic features or predominant inflammatory-reactive changes (HIV-myelopathy)? A comparative morphometric study by immunohistochemistry with special emphasis on apoptosis and PCNA-labeling. 888 51

Hypoplastic myelodysplastic syndromes (h-MDSs) are difficult to distinguish from acquired aplastic anemia (AA) because of the considerable clinical, cytologic, and histologic similarities between these two disorders. Recent studies have suggested that the bone marrow (BM) in AA is characterized by a decreased number of CD34+ cells and reduced expression of proliferating cell nuclear antigen (PCNA), features that have not been associated with MDS. To determine the potential importance of these markers in the differential diagnosis of hypoplastic BM disorders, we immunostained 50 BM biopsy specimens of cytogenetically characterized cases of AA (27) and h-MDS (23). Immunohistochemical staining for CD34 was performed with QBEND10 (Vector, Burlingame, Calif), a monoclonal antibody (MoAb) reactive in routinely processed specimens, while PCNA was assessed by the PC10 MoAb (Dako, Carpinteria, Calif) using a microwave over-based antigen retrieval technique. Bone marrow specimens of h-MDS cases showed statistically higher values of PCNA and CD34 than did those of the AA cases: mean values (+/- SD) of CD34-positive cells in h-MDS, 0.94% +/- 1.1; AA, 0.04% +/- 0.1 (P = .0002); PCNA-positive cells in h-MDS, 43.59% +/- 13.3; AA, 14.80% +/- 6.4 (P < .0001). Our study confirms that AA is characterized by low expression of PCNA in BM and reduced CD34 frequency compared with h-MDS and supports the concept of an early deficiency of stem cells in the former disorder. The results also illustrate how immunostaining permits a simple distinction of these conditions in routinely processed BM biopsy specimens.
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PMID:Hypoplastic myelodysplastic syndromes can be distinguished from acquired aplastic anemia by CD34 and PCNA immunostaining of bone marrow biopsy specimens. 905 74

Clonal expansion of leukemic cells is thought to be due to proliferation in excess of apoptosis. To define and compare proliferation and apoptosis between various leukemias and myelodysplastic syndrome (MDS), we measured proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation as surrogate markers for proliferation and caspase 3 activity and annexin V surface binding as surrogate markers for activation of the apoptotic cascade in patients with MDS, chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). We found high proliferation in bone marrow cells from MDS and CMML as measured by PCNA and BrdU incorporation. The lowest level of proliferation was found in CLL. Apoptosis was also highest in MDS and CMML as measured by annexin V and caspase 3 activity. Unexpectedly, we found no significant difference in proliferation in bone marrow CD34+ cells from various leukemias or MDS. Apoptosis was significantly higher in bone marrow CD34+ cells from MDS and CML in chronic phase as compared to CD34+ cells from AML patients. Our results illustrate differences in proliferation and apoptosis between acute and chronic leukemias and MDS. These differences may have diagnostic and therapeutic implications.
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PMID:Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome. 1200 3


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