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

Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.
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PMID:Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes. 156 60

Fifty percent of patients with the myelodysplastic syndrome, frequently following treatment by radiation or chemotherapy, have prognostically unfavorable deletions of the long arms of chromosomes 5 and 7, or trisomy 8, as have the 25% of patients with acute myeloblastic leukemia where remissions last 6-12 months, and where relapse cannot be prevented. In contrast, patients with prognostically favorable cytogenetics (translocation 15; 17 or 8; 21 or inversion 16) maintenance chemotherapy may prevent relapses. Of chronic myelocytic leukemia patients, 85% can achieve hematological remission with interferon alpha, and 40% a partial cytogenetic remission, which probably delays relapse.
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PMID:Prevention of chemotherapy-induced leukemia and of leukemia relapses. 172 55

Acute myelofibrosis is a rare myeloproliferative syndrome characterized by bone marrow proliferation of atypical megakaryocytes, poor response to conventional leukemic therapy, and a fulminant clinical course. Because alpha interferon exhibits potent antiproliferative effects against megakaryocyte progenitors and human fibroblast cell lines, we treated two patients with acute myelofibrosis or the related syndrome of acute myelodysplasia with myelofibrosis with recombinant human interferon alpha-2a. Patient 1 received a 12-week course of interferon alpha (1-6 x 10(6) IU/d) after failure of two cytarabine-based chemotherapy regimens. Interferon administration resulted in prompt improvement in symptoms, stabilization of leukocyte count, and a reduction in circulating blast forms. Primary treatment with interferon (1-3 x 10(6) IU/d x 4 weeks) in patient 2 produced complete hematologic recovery with restoration of marrow cellularity and reduced marrow fibrosis. Our findings suggest that interferon alpha may have significant activity in the treatment of patients with acute myelofibrosis.
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PMID:Acute myelofibrosis: response to recombinant human interferon alpha-2a. 233 85

We treated 11 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia with natural interferon alpha (human lymphoblastoid interferon; HLBI). HLBI was given at 6-12 X 10(6) u/day i.m. or i.s.c. during induction therapy. Nine patients responded to the treatment, of whom 7 had hematologic remission and 2 had partial remission. Six patients with MDS or hypoplastic leukemia, and 3 patients with overt leukemia from MDS were treated with recombinant interferon gamma (GI-3). GI-3 was given at 0.4 X 10(6) u/m2 of body-surface area per day i.s.c. or i.v. for 4-6 weeks. In 2 patients with RAEB and hypoplastic leukemia, the blast cell count in bone marrow decreased from 8-16% to 2-3% after 4 weeks of administration. In another patient with hypoplastic leukemia, blast cells in the marrow did not decrease, but anemia was improved without transfusion, increasing the bone marrow NCC and erythroblast count. In patients with overt leukemia and CMML, no clinical effect was obtained. Interferons can therefore be offered to patients in a preleukemic state.
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PMID:[Clinical investigation of interferons in the preleukemic state (CML and MDS)]. 313 93

We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.
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PMID:Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis. 752 95

Eighteen patients (pts) with myelodysplastic syndrome (MDS) were treated with thymopentin (TP) (50 mg subcutaneously for 5 days) and recombinant interferon alpha 2a (rIFN alpha 2a) (3 MU/m2 subcutaneously on the sixth day); the courses were delivered every week. Moreover those pts with > or = 10% blasts in the bone marrow were additionally treated with low dose cytosine arabinoside (LDARAc) (20 mg standard dose, subcutaneously, twice a day for seven days every four weeks). Sixteen pts were finally assessable for response. Seven pts (44%) were classified as good responders, 5 (31%) had a PR; the overall response rate (GR+PR) was 75%. Two pts (12.5%) showed stable disease and the 2 remaining (12.5%) had progressive disease. Six pts with an initial moderate anemia never required supportive care before and during the therapy; in contrast to 10 pts who were transfusion-dependent. After six months of therapy 2 pts decreased their transfusional needs by 50% (1 of them did not receive any transfusion over the following six months of therapy); 2 pts needed no packed red cell infusions and 1 pt decreased his transfusional support by 75%. Five pts kept an unchanged supportive care load. The overall median survival was 12.5 months. Therapy was generally well tolerated with acceptable compliance; the most frequently recorded side effects were neutropenia and thrombocytopenia grade 2-3 among the group receiving LDARAc. However no life-threatening infectious episodes or bleeding were observed. TP, rIFN alpha 2a and LDARAc can be safely administered on an outpatient basis to MDS pts and appears to have significant activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recombinant interferon alpha 2a, thymopentin and low doses of cytosine arabinoside for the treatment of myelodysplastic syndromes: a pilot study. 771 40

The p16 protein is a cyclin inhibitor encoded by a gene located in 9p21, which may have antioncogenic properties, and is inactivated by homozygous p16 gene deletion or, less often, point mutation in several types of solid tumors often associated to cytogenetic evidence of 9p21 deletion. We looked for homozygous deletion and point mutation of the p16 gene in acute lymphoblastic leukemia (ALL), where 9p21 deletion or rearrangement are also nonrandom cytogenetic findings. Other hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and myeloma were also studied. Homozygous deletion of the p16 gene was seen in 9 of the 63 (14%) ALL analyzed, including 6/39 precursor B-ALL, 3/12 T-ALL, and 0/12 Burkitt's ALL. Three of the 7 ALL with 9p rearrangement (including 3 of the 5 patients where this rearrangement was clearly associated to 9p21 monosomy) had homozygous deletion compared to 5 of the 55 patients with normal 9p (the last patient with homozygous deletion was not successfully karyotyped). Single stranded conformation polymorphism analysis of exons 1 and 2 of the p16 gene was performed in 88 cases of ALL, including the 63 patients analyzed by Southern blot. Twenty-six of the cases had 9p rearrangement, associated to 9p21 monosomy in at least 12 cases. A missense point mutation, at codon 49 (nucleotide 164), was seen in only 1 of the 88 patients. No homozygous deletion and no point mutation of the p16 gene was seen in AML, MDS, CLL, and myeloma. Homozygous deletion of interferon alpha genes (situated close to p16 gene in 9p21) was seen in only 3 of the 9 ALL patients with p16 gene homozygous deletion, and none of the ALL without p16 gene homozygous deletion. Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy. On the other hand, p16 point mutations are very rare in ALL, and we found no p16 homozygous deletions or mutations in the other hematologic malignancies studied.
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PMID:p16 gene homozygous deletions in acute lymphoblastic leukemia. 783 69

The myelodysplastic syndrome (MDS) and myeloproliferative syndrome (MPS), together with chronic lymphatic leukemia (CLL) are, for the most part, seen in the elderly. Chronic myeloid leukemia (CML), however, is not common in this age group. New treatment for the myelodysplastic syndrome is the use of cytokines, for CLL fludarabine, and 2-chloro-2-deoxy-adenosine (2-CDA). The standard form of treatment for CML and other myeloproliferative syndromes is interferon alpha or hydroxyurea, or a combination of the two.
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PMID:[Leukemias in advanced age. Part 2: Myelodysplastic syndrome and chronic leukemia]. 802 Aug 58

Interferon-alpha has been used as a differentiating agent in the treatment of patients with myelodysplastic syndrome with conflicting results and often significant toxicity. In order to maximize the differentiating effects of this agent and minimize the myelosuppressive effects, a prospective pilot study was initiated utilizing interferon alpha-2a (Roferon A, Roche Laboratories) in the treatment of complicated or poor prognosis myelodysplasia. The study regimen utilized 'mini-dose' interferon alpha-2a at 1 x 10(6) units subcutaneously three-times per week for 16 weeks followed by an 8 week observation period. Nine patients were enrolled between May 1990 and June 1991, of which seven are evaluable. Forty-three percent (3/7) had a partial or clinical response as defined by normalization of one or more of the hemoglobin concentration, white blood cell count, or platelet count, or a decrease in transfusion requirement by > or = 50%. Only one patient was removed from study for interferon-associated toxicity. Mini-dose interferon alpha-2a appears to be an effective regimen for some patients with myelodysplasia which can be administered with minimal toxicity. Further investigation with interferon-alpha for the treatment of myelodysplastic syndrome, at the dosage utilized in this study, is warranted.
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PMID:Mini-dose interferon alpha-2a in the treatment of myelodysplasia. 842 72


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