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)

We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
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PMID:Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. 143 50

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.
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PMID:In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. 195 74

Although it is well recognized that granulocytic sarcoma can cause localized lymphadenopathy, widespread nodal involvement by acute myelocytic leukemia (AML), clinically mimicking non-Hodgkin's lymphoma, has only been previously described twice. We report the clinicopathological, immunological, and cytochemical features of two patients who had widespread, prominent lymphadenopathy secondary to AML as well as concurrent marrow leukemia (M1 and M2). For one patient the lymphadenopathy was the predominant abnormality prompting him to seek medical attention, while the second patient had symptoms of infection following a 9-month history of myelodysplasia. The disease in both patients was aggressive; one patient survived only 1 week and the other survived only 5 weeks after diagnosis. In both cases the granulocytic sarcoma was confirmed by cytochemistry studies (naphthol ASD-chloroacetate esterase on tissue sections and myeloperoxidase on imprint smears), and electron microscopy, including morphology (both cases) or ultrastructural localization of myeloperoxidase (case 2). Non-specific esterase activity was not detected in either patient's blasts, although serum lysozyme was elevated in both cases. Immunological studies revealed reactivity of both patients' cells with panleukocyte, MY4, MY7, OKM-1, and Leu-M1 monoclonal antibodies and with alpha-1-antitrypsin and muramidase antibodies. The cells of one of these patients also reacted with anti-S-100 protein. Although the cytochemical studies indicated that both cases exhibited only myeloid differentiation, the immunological markers suggested that the tumor cells possessed some features of monocytes, perhaps explaining their propensity for widespread tumor formation. Morphological, immunological, cytochemical, and ultrastructural methods of diagnosing granulocytic sarcoma are presented.
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PMID:Acute myelocytic leukemia manifested by prominent generalized lymphadenopathy: report of two cases with immunological, ultrastructural, and cytochemical studies. 345 62

A new hematopoietic cell line derived from a patient with Philadelphia chromosome (Ph1)-negative myeloblastic leukemia arising from a form of myelodysplastic syndrome (MDS) is described. This cell line, designated TMM, consists of immature cells with the morphological characteristics of young myeloblasts and grows in suspension culture with a doubling time of about 30 hours. By cytochemical analysis the cultured cells were positive for acid phosphatase. They were free of the Epstein-Barr virus-associated nuclear antigen as well as terminal deoxynucleotidyl transferase. Further phenotypic analysis revealed the expression of the myelomonocytic-specific antigen Leu-M1 and receptors for the Fc portion of IgG. Partial differentiation of these cells could be induced by dimethyl sulfoxide, tetradecanoyl phorbol acetate, or hypoxanthine and resulted in cells of the myeloid series expressing lysozyme and receptors for the C3b complement protein. The karyotype was 46,XY, lacked the Ph1 chromosome, and displayed no abnormalities at the light microscopic level. No rearrangement of the bcr-c-abl gene complex was found. This cell line should be useful for studying an important type of the heterogeneous population constituting Ph1-negative myeloblastic leukemia, arising in this instance from MDS, as well as for studying differentiation and proliferation of human pluripotent stem cells.
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PMID:Establishment and characterization of a human myeloid cell line from Philadelphia chromosome-negative myeloblastic leukemia arising in a patient with myelodysplastic syndrome. 347 6

The proliferation and differentiation effects of the synthetic retinoid TTNPB and of 13-cis retinoic acid (RA) on hemopoietic progenitors from bone marrow of myelodysplastic syndrome (MDS) patients were compared. The addition of TTNPB or RA to culture plates containing MDS patient's marrow cells stimulated myeloid colony (CFU-C) growth and caused a significant increase in granulocytic colonies (CFU-G). In the presence of RA the increase in CFU-G was statistically insignificant. Cellular differentiation studies in liquid suspension culture revealed that the two retinoic acid analogues cause a marked decrease in immature granulocytes and an increase in mature granulocytes. There was further an increase in the number of cells that reacted positively with monoclonal antibodies (McAb) binding specifically to granulocytes (B4,3,B13,9 and Leu M4) and a decrease in the percentage of cells reacting with the McAb against Ia-like determinants. These findings indicate that TTNPB is as active as RA in stimulating the growth of hemopoietic progenitors from MDS patients and in enhancing granulocytic differentiation in liquid culture.
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PMID:In-vitro growth and differentiation of marrow cells from myelodysplastic patients in the presence of a retinoidal benzoic acid derivative. 361 48

The effect of retinoids on cell differentiation in the myelodysplastic syndrome was studied in short-term liquid cultures of bone marrow from 13 patients. After incubation with 13-cis-retinoic acid there was a significant decrease in the percentages of promyelocytes and in Leu-M3-binding cells. Lue-M3 is mainly a monocyte marker, and retinoids thus seem to induce a shift from monocytoid to myeloid differentiation. Patients with refractory anemia with an excess of blasts responded the most, and did also show a significant decrease in OKIa1-binding cells. Etretinate, on the other hand, did not show any differentiation-inducing activity. The results support earlier reports that retinoic acid might be useful in the treatment of the myelodysplastic syndrome. Whether this in vitro technique offers a possibility to predict the clinical outcome remains to be shown.
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PMID:Effects of retinoids on in vitro differentiation of bone marrow cells in the myelodysplastic syndrome. 370 9

f-Met-Leu-Phe-stimulated luminol-enhanced chemiluminescence was found to be repeatedly defective in some MDS patients. This defect was not attributed to myeloperoxidase deficiency, nor to a defect in NADPH oxidase function, because PMA chemiluminescence was found to be normal in these individuals. An arbitrary value of 7 mV (half the mean control value) was chosen to subdivide the group: MDS patients with values < 7 mV had a mean f-Met-Leu-Phe chemiluminescence response of 2.5 +/- 0.5 compared to MDS patients with values > 7 mV who had a mean response of 15.6 +/- 1.6 mV, P < 0.01 (healthy controls 14 +/- 2 mV). The characteristics of the f-Met-Leu-Phe receptor and initial calcium flux results suggested that the receptor itself was normal in number and function in low f-Met-Leu-Phe responders. The rate of superoxide generation, which is calcium-dependent, was also found to be in the normal range in low f-Met-Leu-Phe responders, although total superoxide production was reduced in some of these patients. When MDS neutrophils with a low f-Met-Leu-Phe response were stimulated with PMA, chemiluminescence was normal, suggesting normal activity of the NADPH-oxidase complex. Furthermore, myeloperoxidase activity was reduced in only three out of the 11 low f-Met-Leu-Phe responders. Following priming with GM-CSF, f-Met-Leu-Phe chemiluminescence was 27 +/- 1.6 mV in low f-Met-Leu-Phe responders compared to controls (87.7 +/- 11 mV, P < 0.005). Thus, although responses were improved, they were not as marked as in control neutrophils. These data suggest that a subgroup of MDS patients have a low f-Met-Leu-Phe chemiluminescence response which is not due to a defect in the f-Met-Leu-Phe receptor or oxidase activity, and in the majority of cases MPO activity is normal. Initial patient survival data suggest that these patients may have an increased risk of infective mortality. It is proposed that defective f-Met-Leu-Phe chemiluminescence results from a putative defect in cell-signalling mechanism upstream of PKC, and GM-CSF priming only partially improves responsiveness.
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PMID:Identification of a subgroup of myelodysplastic patients with a neutrophil stimulation-signalling defect. 791 69

Granulocytic sarcoma (GS) is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. Most GS reported in large series were not associated with overt acute myelogenous leukemia. Gastric perforation occurred during prednisolone therapy in a 72-year-old Japanese male with a four-month history of a myelofibrosis-like state. Subtotal gastrectomy was performed for a suspected gastric ulcer perforation. Gastric histologic, immunohistochemical and cytochemical examination revealed diffuse infiltration by sheets of myeloblasts and promyelocytes with scant or moderately abundant cytoplasm including a few eosinophilic myelocytes. Bone marrow study done in one month after the operation disclosed refractory anemia with excess of blasts (RAEB). Leukemic transformation occurred two months later, and a subcutaneous tumor appeared on the forehead. The forehead tumor predominantly consisted of myeloblasts without evidence of maturation. Both the stomach and forehead tumors were examined immunohistochemically with a panel of monoclonal antibodies (LCA, L26, MT1, UCHL1, OPD4, LN-1, LN-2, LN-3, MB1, Leu-M1, PM) and polyclonal antibodies (lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 protein, lactoferrin), as well as naphthol-ASD-chloroacetate esterase staining to investigate and characterize the reliable marks for GS, and the patient was diagnosed as GS. We found that gastric GS may occur in a myelofibrosis-like state followed by RAEB of myelodysplastic syndrome and that naphthol-ASD-chloroacetate esterase staining and immunohistochemical detection of MT1, lysozyme, and alpha 1-antitrypsin were the most reliable markers for confirming the diagnosis of GS.
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PMID:Unsuspected gastric granulocytic sarcoma in a patient with myelodysplastic syndrome. 870 73

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, APO2L) has been shown to induce apoptosis in a number of tumor cell lines as well as in some primary tumors whereas cells from most normal tissues are highly resistant to TRAIL-induced apoptosis. We have studied the susceptibility of primary malignant and normal bone marrow hematopoietic progenitors to TRAIL-induced apoptosis. Extracellular domain of human TRAIL with N-terminal His(6) tag (His-TRAIL, amino acids 95-281) was produced in E. coli and its apoptosis-inducing ability was compared with the leucine-zipper containing TRAIL, LZ-TRAIL. Both variants of TRAIL had the same apoptosis-inducing ability. Clonogenic progenitor assays showed that His-TRAIL significantly reduced the number of myeloid colonies (CFU-GM) and clusters from patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndromes (MDS). His-TRAIL had no negative effect on the number of CFU-GM colonies and clusters derived from bone marrow cells of AML patients in complete remission, and lymphoma patients without bone marrow involvement, as well as those derived from normal cord blood cells. Moreover, we found that normal human stem cells treated with high doses of His-TRAIL maintain a repopulating potential when transplanted into NOD/SCID mice. To conclude, our data document that TRAIL does not affect normal human hematopoiesis but suppresses the growth of early primary leukemia and myelodysplasia progenitors.
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PMID:TRAIL (Apo2L) suppresses growth of primary human leukemia and myelodysplasia progenitors. 1184 Feb 65

Myelodysplasia/acute myeloid leukemia (MDS/AML) is characterized by a t(3;5)(q25.1;q34) chromosomal translocation that forms a fusion gene between nucleophosmin (NPM) and MDS/myeloid leukemia factor 1 (MLF1). We identified a novel protein, MLF1-interacting protein (MLF1IP), that specifically associates with MLF1 by yeast two-hybrid analysis and in pulldown assays, and colocalizes with it in both the nuclei and cytoplasm of cells. The MLF1IP gene locus is at chromosome 4q35.1 and is composed of 14 exons spanning 75.8 kb of genomic DNA. The MLF1IP cDNA encodes a 46-kDa protein that contains two bipartite and two classical nuclear localization signals, two nuclear receptor-binding motifs (LXXLL), two leucine zippers, two PEST residues and several potential phosphorylation sites. MLF1IP transcripts are expressed in a variety of tissues (e.g. fetal liver, bone marrow, thymus and testis). MLF1IP appears to be a lineage-specific gene whose expression is confined exclusively to the CFU-E erythroid precursor cells, but not in mature erythrocytes. These observations, together with previous data demonstrating a role for MLF1 in suppressing red cell maturation, suggest a possible role for MLF1IP and MLF1 deregulation in the genesis of erythroleukemias.
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PMID:cDNA cloning and characterization of a novel gene encoding the MLF1-interacting protein MLF1IP. 1511 1


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