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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical studies were performed with monoclonal antibodies (MAbs) reactive on paraffin embedded bone marrow biopsies in 19 patients with myelodysplastic syndromes, 8 of them during r gamma-interferon treatment. CD15 MAbs stained mature myeloid cells predominantly located close to the bone marrow trabeculae. Anti-gpIIIa MAbs permitted precise identification of megakaryocytic cells including precursors and dysplastic megakaryocytes. Labelling with CD45 and CD68 MAbs, recognizing lymphocytes and macrophages respectively, was intense in patients in steady state, but progressively decreased during leukemic transformation. Increase in CD45+ and/or CD68+ cells was also observed in most bone marrow biopsies after 3 months of r gamma-interferon therapy.
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PMID:Immunohistochemical evaluation of bone marrow biopsies in myelodysplastic syndromes. 181 62

We have established a new nonlymphoid leukemic cell ine from a patient with myelodysplastic syndrome (MDS), which progressed to overt leukemia. The parental cell line and a subline derived from this line have absolute dependency on several cytokines for their long-term survival and growth. The parental line designated F-36P requires granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) for continuous growth, while a subline designated F-36E can be maintained in the presence of erythropoietin (Epo) alone. When these cytokines are depleted, both the parental and the subline cells die within several days, even in medium supplemented with fetal calf serum (FCS). F-36E, maintained in the presence of Epo, constitutively synthesizes hemoglobin at a significant level. F-36P, which is usually maintained in the presence of GM-CSF or IL-3, can be induced to synthesize hemoglobin when GM-CSF or IL-3 is substituted by Epo. The surface marker profile shows that the F-36P cells are positive for the leukocyte common antigen (CD45) and some common multilineage markers such as CD13, CD33, and CD34, and negative for T- and B-cell antigens and mature myelomonocytic antigens. However, some monoclonal antibodies recognizing erythroid and platelet glycoproteins react with these cells. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in a multipotent stem cell. It is also evident that the F-36 cells can be induced to differentiate into the erythroid lineage in the presence of Epo. This, to our knowledge, is the first description of a human leukemic cell line that can be stimulated to synthesize hemoglobin by Epo.
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PMID:Establishment and erythroid differentiation of a cytokine-dependent human leukemic cell line F-36: a parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3, and a subline requiring erythropoietin. 183 51

Two anti-nerve growth factor receptor (LNGFR or p75NGFR) antibodies, Me20.4 and Me8211, label stromal cells with dendritic features in fresh smears and in formalin-fixed, paraffin-embedded human bone marrow (BM). The LNGFR+ cells have an oval nucleus, a scanty cytoplasm with long dendrites that intermingle with the hematopoietic cells, line the abluminal side of sinus endothelial cells, and provide the scaffold for the hematopoietic marrow. At the electron microscopy level, the immunogold tag labels the body and the long branching dendrites of fibroblast-like cells with scanty cytoplasm containing mitochondria, endoplasmic reticulum, and dense bodies. The LNGFR+ cells are positive for alkaline phosphatase, reticulin, collagen III, vimentin, TE-7, and CD13 but negative for endothelial (vWF, CD34, Pal-E), neural (CD56, neurofilament) and leukocyte markers (CD45, CD68). The LNGFR+ stromal cells appear in the fetal BM before the hematopoietic activity begins, originate from the vessel adventitia, and radiate in the Bm cavity. Long-term BM culture (LTBMC) in vitro contain LNGFR+ stromal cells. We document the presence of RNA message for the low- (LNGFR) and the high-affinity NGF receptor (NTRK1) by using RT-PCR on fresh BM aspirate and on LTBMC. BM biopsies from patients with hematologic fibrogenic diseases and in cytokine-treated cancer patients are evaluated for LNGFR+ cells: the amount of stained cells is correlated with the traditional reticulin stain in cases of myelofibrosis, therapy-related myelodysplasia, leukemia, and detected an increase of stromal cells in cytokine-treated patients. The anti-LNGFR antibodies represent a specific membrane marker for the adventitial reticular cells (ARC) of the human marrow and allow precise evaluation and quantitation of this important BM microenvironment component in vivo and in vitro.
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PMID:Bone marrow stroma in humans: anti-nerve growth factor receptor antibodies selectively stain reticular cells in vivo and in vitro. 768 1

This article describes a procedure for performing routine three-color flow cytometric analysis for acute leukemia on lysed whole bone marrow preparations. This technique uses the combination of CD45 intensity and right-angle light scatter (RALS) to distinguish leukemic cells from normal lymphocytes, monocytes, neutrophils, eosinophils, and nucleated red blood cells. On this display, leukemic cells occupy a unique blast region characterized by intermediate CD45 density and low RALS, which, in normal marrows, contains less than 5% of the total cells. This approach was applied to 39 cases of acute leukemia and 8 cases of myelodysplasia or myeloproliferative disorders. The estimate of blasts by flow cytometric analysis was correlated highly with morphologic leukemic cell counts over a wide range. Moreover, the pattern seen on the CD45-RALS display was different for different French-American-British subtypes of leukemia, suggesting that this pattern might be useful for categorization. When CD45-peridin chlorophyll alpha protein was combined with other pairs of fluorescein isothiocyanate- and phycoerythrin-conjugated reagents, it was possible to set an analysis window on the leukemic blasts and display dual-parameter (ie, green vs. red fluorescence) data regarding expression of two additional markers on the leukemic population. This gating strategy was superior to traditional forward-angle versus RALS displays in that it did a better job of isolating the leukemic cells analytically.
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PMID:Immunophenotyping of acute leukemia by flow cytometric analysis. Use of CD45 and right-angle light scatter to gate on leukemic blasts in three-color analysis. 824 93

We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.
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PMID:Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome. 861 53

The case history of a 70-year-old man with myelodysplastic syndrome terminated into acute leukemia in 22 months is presented. The leukemic cells exhibited multifocal acid phosphatase positivity and expressed TdT, CD45, CD34 and HLA-DR but not myeloid, monocytic or megakaryocytic differentiation antigenes. The genotypic analysis revealed clonal immunoglobulin heavy chain gene rearrangement. These phenotypic and genotypic analyses of the blastic cell population suggest that myelodysplastic syndrome may transform to pure acute lymphoblastic leukemia of B-cell origin.
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PMID:Phenotypic and genotypic analyses of blastic cell population suggest that pure B-lymphoblastic leukemia may arise from myelodysplastic syndrome. 958 74

Disease recurrence following successful bone marrow transplantation remains a major impediment in the management of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A variety of monoclonal antibodies that deliver drugs or toxins to the site of activity, have been used in an attempt to augment marrow transplantation. Examples of three different monoclonal antibody techniques (naked antibody, drug antibody conjugations, and radiolabeled antibodies) are discussed. CD33 is an attractive antigen to use as a target for treating AML because it is present on most AML cells. Naked antibodies are limited in their ability to kill tumor cells, although studies to date suggest there may be a role in antileukemic therapy for unlabeled anti-CD33 humanized M195 antibody after the tumor burden has been reduced by chemotherapy. Calicheamicin, a novel and toxic drug moiety conjugated to anti-CD33 antibody, is currently under investigation in patients with refractory or relapsed AML. Results from a Phase I investigation were encouraging. Three different radiolabeled monoclonal antibodies have been evaluated in Phase I/II studies--131I-labeled anti-CD33 (p67) antibody, 213Bi-labeled humanized M195 antibody, and 131I-anti-CD45 antibody. CD45 is a cell-surface antigen broadly expressed by all circulating leukocytes and lymphocytes. Initial studies demonstrated that substantially greater doses of radiation could be delivered to targeted organs compared with nontargeted organs using 131I-anti-CD45 antibody. This approach offers the potential for augmenting leukemia therapy without increased risk of toxicity.
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PMID:Immunotherapy in acute myelogenous leukemia and myelodysplastic syndrome. 977 93

Apoptosis of haemopoietic cells in the marrow of patients with myelodysplastic syndrome (MDS) has been suggested as a mechanism for peripheral cytopenias. We determined the expression of Fas (CD95), Fas-Ligand (Fas-L) and TNF-alpha factors known to be involved in apoptosis, in the marrow of 44 patients with MDS and characterized their functional relevance in in vitro assays of haemopoiesis. Multidimensional flow cytometry revealed phenotypically aberrant blasts as defined by orthogonal light scatter and CD45 expression in the marrow of 24/44 patients. Among those blasts Fas expression was increased on CD34-positive cells and on cells co-expressing HLA-DR. In addition, Fas-L was expressed on some CD34+ cells of MDS patients but was never detected on CD34+ cells in normal marrow. Fas and Fas-L mRNAs as well as mRNA for TNF-alpha, known to increase Fas expression in normal marrow, were up-regulated in patients with MDS. TNF-alpha protein and sTNF-R1 levels in marrow plasma were higher in MDS patients than in controls (P<0.002 and <0.003, respectively). However, results were dependent upon disease category: TNF-alpha levels were significantly higher in patients with refractory anaemia (RA) than in patients with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-T) (P=0.043). Conversely, the proportion of Fas-L-positive cells was lowest in patients with RA (P=0.037). In marrow cultures, Fas-Ig, rhuTNFR:Fc or anti-TNF-alpha antibody, by blocking Fas or TNF mediated signals, respectively, significantly increased the numbers of haemopoietic colonies compared to untreated cells (P<0.001, P<0.003, P<0.001, respectively). These results show significant dysregulation in the expression of TNF-alpha, Fas and Fas-L in the marrow from MDS patients. Altered expression of these molecules appears to be of functional relevance in the dysregulation of haemopoiesis in MDS and may be amenable to therapeutic interventions.
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PMID:A role for tumour necrosis factor-alpha, Fas and Fas-Ligand in marrow failure associated with myelodysplastic syndrome. 979 6

Patients with unexplained cytopenias often present a diagnostic dilemma with minimal morphologic or cytogenetic changes to identify the underlying disease process. We have used multidimensional flow cytometry in a study of patients with cytopenias and found that this technology established, changed, or refined the diagnosis in 17/121 patients. Using the flow cytometric technique of CD45 and right angle light scatter (SSC) gating with two additional markers in a three-color analysis, eight of 121 patients were found to have hairy cell leukemia (HCL), in the absence of definitive morphologic findings of HCL. Two additional patients were found to have non-Hodgkin's lymphoma (NHL). Myeloid abnormalities, myelodysplasia (MDS) or acute leukemia was detected in seven of 56 patients with unexplained pancytopenia. Six of 65 patients identified with cytopenias resulting from lymphoid neoplasms had been referred for bone marrow transplantation (BMT) with a presumptive diagnosis of MDS, with subsequent deferral of BMT upon correct diagnosis. The screening technique is incorporated into an extensive immunophenotyping scheme to identify hematopoietic abnormalities using multidimensional flow cytometry (MDF). HCL cells (detected as low as 1.3%) reside in the same position as normal monocytes in the CD45 and SSC plots but could be distinguished from monocytes based on the expression of HLA-DR without CD11b, and expression of CD19. Further phenotyping of the abnormal population confirmed immunoglobulin light chain restriction, CD11c, and CD25 expression. Non-Hodgkin's lymphoma was detected as aberrant mature lymphocytes expressing B lymphoid markers, CD5 and light chain restriction. Myeloid abnormalities were identified in the myeloblast or maturing myeloid cell fractions. The flow cytometric scheme described can be used in primary diagnosis. The technique is definitive, sensitive, and stresses the importance of distinguishing lymphoid from myeloid etiology of cytopenias.
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PMID:Occult B cell malignancies can be detected by three-color flow cytometry in patients with cytopenias. 984 32

In order to determine the relationship between bone marrow (bm) endosteal cells (EDC) and hemopoietic progenitors, we have analyzed the immunophenotype of EDC using various antibodies (Ab) against mesenchymal antigens. The Ab were applied on paraffin sections of normal bm (iliac crest, n=17; talus, n=1; phalanx, n=1), myeloregenerative bm (after chemotherapy), and hematologic disorders (acute myeloid leukemia (AML), n=8; chronic myeloid leukemia (CML), n=6; myelodysplastic syndromes (MDS), n=14; severe aplastic anemia (SAA), n=4; essential thrombocythemia (ET), n=2; idiopathic (primary) osteomyelo-fibrosis (IMF), n=1; polycythemia vera (PV), n=1). In normal bm, EDC were found to react with Ab against vimentin, tenascin, alpha-smooth muscle actin, osteocalcin, CD51, and CD56, but did not react with Ab against CD3, CD15, CD20, CD34, CD45, CD68, or CD117. An identical phenotype of EDC was found in AML, MDS, SAA, ET, IMF, PV, myeloregenerative bm, and peripheral bones lacking active hemopoiesis (talus, phalanx). In patients with CML, EDC reacted with Ab to CD51, but did not react with Ab to CD56. Based on their unique antigen profile, EDC were enriched from normal bm by enzyme digestion and cell sorting. However, these enriched cells (CD56+, CD45-, CD34-) did not give rise to hemopoietic cells under the culture conditions used, i.e. in the presence of the growth factors IGF-1, bFGF, SCF, IL-3, and GM-CSF Together, our data do not support the hypothesis that EDC are totipotent mesenchymal progenitors giving rise to hemopoietic cells.
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PMID:Immunophenotypic characterization of human bone marrow endosteal cells. 1039 6


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