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 studied the expression of IL 6 gene in 49 patients, including 21 chronic myelomonocytic leukemias (CML), 9 other myelodysplastic syndromes (MDS), 18 acute myeloid leukemias (11 M2 or M3 and 7 M4 or M5) and 1 case of acute biphenotypic lymphoid monocytic leukemia. IL 6 was found expressed only in the latter patient and in one patient with M5 acute myeloid leukemia. DNA analysis by Southern blot revealed no rearrangement in these 2 patients and in 10 of the other patients who showed no IL 6 expression. These results do not support an autocrine role for IL 6 in CMML or in other MDS. In acute myeloid leukemias, if expressed by leukemic cells, IL 6 seems to be restricted to cases with a monocytic component, although the number of patients was too small to draw any definite conclusion.
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PMID:Expression of the interleukin 6 gene in acute myeloid leukemia and myelodysplastic syndromes: a report on 49 cases. 221

We have identified an identical reciprocal translocation between the long arms of chromosomes 3 and 21 with breakpoints at bands 3q26 and 21q22, [t(3;21)(q26;q22)], in the malignant cells from five adult patients with therapy-related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Primary diagnoses were Hodgkin's disease in two patients and ovarian carcinoma, breast cancer, and polycythemia vera in one patient each. Patients had been treated with chemotherapy including an alkylating agent for their primary disease 1 to 18 years before the development of t-MDS or t-AML. We have not observed the t(3;21) in over 1,500 patients with a myelodysplastic syndrome or acute myeloid leukemia arising de novo or in over 1,000 patients with lymphoid malignancies. We have previously reported that the t(3;21) occurs in Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Thus, the t(3;21) appears to be limited to t-MDS/t-AML and CML, both of which represent malignant disorders of an early hematopoietic precursor cell. These results provide a new focus for the study of therapy-related leukemia at the molecular level.
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PMID:t(3;21)(q26;q22): a recurring chromosomal abnormality in therapy-related myelodysplastic syndrome and acute myeloid leukemia. 226 51

Clonal chromosome abnormalities are found in more than half the patients with hematologic malignancies. Karyotype is an independent prognostic factor in these patients. Cytogenetic findings correlate significantly with morphologic, immunologic, and clinical features as well as response to treatment, remission duration, and survival. The number of different cytogenetic abnormalities is enormous; however, many cytogenetic findings frequently occur in a given disease (e.g., abnormalities of 5 or 7 in 75% to 90% of patients with therapy-related AML). Some abnormalities are found only in myeloid malignancies, for example, the t(8;21)(q22;q22) and rearrangements of chromosome 16q22, both of which have a good prognosis. Other abnormalities usually are found in both myeloid and lymphoid malignancies, for example, the t(4;11)(q21;q23) and t(9;22)(q34;q11), both of which have a poor prognosis. The Human Gene Mapping Conferences have compiled much cytogenetic data and produced several interesting correlations in myeloid malignancies: rearrangements of 3q21-26 with myeloid proliferations associated with environmental exposure (similar to abnormalities of 5q, 7q, 12p, and 17q), aberrations of 12p, 11q13 and 11q23 with both myeloid and lymphoid disorders, and the lack of myeloid involvement and abnormalities of chromosomes 14 and 18. In conclusion, cytogenetic analysis of neoplastic cells at diagnosis for patients with MDS, AML, and SAML is required for appropriate diagnosis and treatment. The use of chromosome abnormalities to separate patients into high- and low-risk groups eventually may allow us to be more effective in selecting curative therapy.
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PMID:Chromosomal abnormalities in myelodysplastic syndromes and acute myeloid leukemia. 227 73

The myeloid growth factors are a promising new class of therapeutic agents with the potential for broad clinical application. Four recombinant myeloid growth factors, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-3 are available for clinical trials. GM-CSF has been studied in leukopenia related to acquired immunodeficiency syndrome (AIDS), aplastic anemia, and myelodysplasia, as well as in patients receiving chemotherapy and those undergoing autologous bone marrow transplantation. In these trials, GM-CSF was demonstrated to increase the number of neutrophils, eosinophils, and monocytes with corresponding bone marrow changes. Toxicity is dose-related, and maximum tolerated dosages are in the range of 16 to 32 micrograms/kg/day. The effects of daily subcutaneous administration of GM-CSF appear to be similar to those of intravenous (IV) administration. G-CSF, studied mainly in the treatment of neutropenia following cytotoxic chemotherapy, was found to decrease the duration of severe neutropenia as well as the risk of infections. G-CSF causes prominent increases in neutrophil levels without affecting eosinophils or monocytes. Associated toxicity is minimal, and subcutaneous administration is efficacious. Preliminary evidence suggests that G-CSF may also have a therapeutic role in indolent lymphoid neoplasms complicated by neutropenia. Administration of natural M-CSF to patients receiving chemotherapy and those with chronic childhood neutropenia has shown modest neutrophil increases. Preclinical data on IL-3 suggest that this agent increases neutrophils, eosinophils, basophils, reticulocytes, and possibly platelets.
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PMID:Clinical applications of the myeloid growth factors. 247 Dec 74

Clinical trials of recombinant biologic agents have resulted in new treatment options for hematologic, oncologic, and cardiologic disorders. These agents include the interferons, recombinant human erythropoietin (r-HuEPO), colony-stimulating factors (CSFs), interleukins (ILs), and tissue plasminogen activator (t-PA). Interferon alfa has proven efficacious in treating certain hematologic malignancies and solid tumors and has recently been indicated for acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Treatment with r-HuEPO has relieved the chronic anemia of hemodialysis patients. Recombinant human granulocyte CSF (G-CSF) or human granulocyte macrophage CSF (GM-CSF) has been used to treat patients after autologous bone marrow transplantation for lymphoid or solid malignancies, resulting in increased production of granulocytes and platelets. G-CSF and GM-CSF have been used to treat aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with AIDS. In patients with evolving myocardial infarction, the recombinant agent t-PA has proved more efficacious than streptokinase in terms of average coronary artery patency rates and survival rates in patients with evolving myocardial infarction. While these agents all offer promising therapeutic advances, the expenses associated with developing and testing biotherapeutic substances have resulted in high treatment costs. Since in many instances investigational therapy is the best treatment option available, physicians, patients, the pharmaceutical industry, the government, and insurance carriers must work together to ensure that these therapies are financially available to those in need.
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PMID:New directions in hematologic biotherapy. 247 3

We used the Amersham radioimmunological method to measure plasma 1 alpha 25-dihydroxyvitamin D3 (calcitriol) levels in patients presenting with one of the following diseases: (i) non-acute myelodysplastic syndrome (39 cases); (ii) acute myeloid leukaemia in blastic phase (43 cases) or in complete remission (15 cases) and (iii) acute lymphoid leukaemia in blastic phase (11 cases). All patients had normal metabolic functions. Compared with our standard laboratory values (15-35 pg/ml), the results of these assays were related to the type of pathology or, in patients with acute myeloid leukaemia, to the stage of the disease (p less than 0.001). Moreover, the mean plasma calcitriol values differed according to the type of pathology (p less than 0.003). Patients with acute myeloid leukaemia in blastic phase had a low level of calcitriol as compared with controls (p less than 0.05) and with patients with acute myeloid leukaemia in complete remission (p less than 0.001) whose calcitriol levels were never low. In contrast, there was no significant difference between controls and patients with myelodysplastic syndrome or acute lymphoid leukaemia in blastic phase. This study demonstrates the usefulness of plasma calcitriol assays in malignant blood diseases where low values in certain types of leukaemia would incite to include calcitriol in therapeutic regimens.
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PMID:[1 alpha 25-dihydroxyvitamin D3 (calcitriol) and malignant hemopathies. Decreased serum levels in acute leukemia: preliminary results]. 248 81

In this paper we review our experience with HIV-related thrombocytopenic purpura (TP) in 24 patients seen from October, 1985 through April, 1988: the median follow-up was 16 months (range 3-32). All patients belonged to risk groups for AIDS and intravenous drug abusers represented 83% of the entire cohort. The male/female ratio was 4, and most of the patients were Walter Reed stage 3. The mean value of platelets at diagnosis was 33 x 10(9)/liter (range 6-120), and half of the patients had severe thrombocytopenia with hemorrhagic symptoms. Anemia and/or neutropenia were concomitant with TP in 21% and 17% of cases; four cases had pancytopenia. Marrow pictures showed megakaryocytic hyperplasia in 68% of cases; myelodysplasia or hypoplasia were observed in 14% and 18% of patients, respectively; lymphoid aggregates were present in two cases. Antiplatelet antibodies and circulating immune complexes were detected in 40% and 50% of cases, and the mean T4/T8 ratio was 0.9 (range 0.4-1.8). Half of the patients did not require specific therapy due to lack of bleeding; however no spontaneous reversions to normal platelet values occurred. The response to steroids and to immunoglobulins (either high-dose or anti-D) was good but temporary, and required maintenance therapy. The 2-year actuarial risk of evolution into overt AIDS was 30%, with a crude rate of 4 cases over 365 person-months at risk. The events which determined AIDS were opportunistic infections in two cases, Kaposi's sarcoma and malignant lymphoma in the other two. A comparison with the features of idiopathic TP is made and hypotheses regarding the pathogenetic mechanisms are discussed.
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PMID:HIV-related thrombocytopenic purpura: a study of 24 cases. 249 84

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.
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PMID:Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin. 256 24

Bone marrow trephines from 31 patients with an initial diagnosis of myelodysplastic syndromes (MDS) were examined and analyzed histologically and immunohistochemically. In those cases terminating in overt leukemia (6/31, 19%), the number of bone marrow mast cells was significantly reduced, compared with those which did not evolve to overt leukemia. The bone marrow lymphoid cells that may participate in immunosurveillance against the proliferation of blast cells were also significantly reduced in cases terminating in overt leukemia. However, S-100 protein-positive cells, which include histiocytes and suppressor T-cells, were increased in cases terminating in overt leukemia. The results indicated that examination of the bone marrow to determine the proportions of mast cells and lymphoid cells which may be involved in host defense systems may be useful in predicting the evolution to overt leukemia in MDS. In the present series, patients with a hypocellular marrow (5/31, 16%) did not progress to overt leukemia and had a significantly lower bone marrow reticulin content, a significantly lower megakaryocyte count, a relatively higher mast cell count and a significantly higher lymphoid cell count than those with a normocellular or hypercellular marrow. These findings may reflect the initial features of MDS or, possibly, that hypocellular MDS is an independent entity with a low potential for blastic proliferation.
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PMID:Bone marrow analysis of the myelodysplastic syndromes: histological and immunohistochemical features related to the evolution of overt leukemia. 256 49

We reviewed 213 consecutive adult pancytopenic patients to determine the frequency of underlying pathology, to analyze our diagnostic procedure, and to determine the value of peripheral blood data for diagnosis. Pancytopenia was defined as the association of hemoglobin level below 12 g/dl in males and 11.5 g/dl in females, leukopenia below 4 x 10(9)/L, and thrombocytopenia below 150 x 10(9)/L. The bone marrow aspirates were normo- or hypercellular in 140 cases (66%). Bone marrow biopsies, performed in 93 cases, documented the presence of myelofibrosis in 67 cases. Aplastic anemia was diagnosed in 10% of the cases. Malignant myeloid disorders (acute myeloid leukemias, myelodysplastic syndromes, acute myeloid disorders with myelofibrosis) represented 42% of the cases and various malignant lymphoid disorders 18%. Vitamin deficiencies accounted for 7.5% and nonhematological pathology 10% of the cases. The bone marrow aspirate was sufficient for the diagnosis in 55% of the cases, and the trephine biopsy was necessary in 30%. In the remaining cases, other complementary tests were necessary to achieve final diagnosis. A discriminant analysis, focused on the hemogram data, showed that parameters obtained by analysis of blood smears were helpful for the diagnosis, especially the presence or absence of blast cells and/or of abnormal lymphoid cells.
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PMID:Adult patients presenting with pancytopenia: a reappraisal of underlying pathology and diagnostic procedures in 213 cases. 262 15


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