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)

Loss of the Y chromosome is a feature of haematologically normal bone marrow in elderly males, but it is also found in haematological malignancy. We describe -Y as the sole karyotypic abnormality in 147 cases (66 from 802 unselected cases and a further 81 cases selected for -Y) with the following diagnoses: no haematological malignancy (N), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and myeloproliferative disorder (MPD). The frequency of -Y in the 802 unselected N, MDS, and AML cases was 7.7%, 10.7%, and 3.7%, respectively. It could not be evaluated in MPD because there were too few cases. In N and MDS cases the frequency increased in a similar fashion over the age of 60 years. The 147 -Y cases showed a similar increase in distribution with advancing age in all four clinical categories. The degree of loss of Y (% -Y cells per patient) increased with age in N and MPD patients but not in those with MDS or AML. This study suggests that in elderly men -Y is not indicative of malignancy and should not be considered as a marker of the malignant clone.
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PMID:Loss of the Y chromosome from normal and neoplastic bone marrows. United Kingdom Cancer Cytogenetics Group (UKCCG) 138 66

The karyotypes of 98 patients between the ages of 8 and 81 years with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloid leukemia (CML) are presented. Although the well-described cytogenetic abnormalities associated with particular FAB subtypes in the West were observed, certain important local differences were noted. In ALL, hyperdiploidy was rarely observed, whereas the Philadelphia chromosome was observed in 50% of abnormal karyotypes. In AML, the t(8;21) was infrequently observed in M2 case, whereas trisomy 4 and 6, rarely reported elsewhere, formed 12% of the abnormal cases. In MDS, the incidence of -5/5q- and/or -7/7q- was 83% of cases with aberrant cytogenetic findings. Neither i(17q) nor an extra Ph was seen in 26 cases of CML including 9 cases of accelerated phase/blast crisis. In addition, previously unreported cytogenetic abnormalities occurring as single cases are presented. These findings are discussed in the context of geographical heterogeneity of chromosomal abnormalities in leukemia and emphasize the importance of continued epidemiologic studies of cytogenetics in hematologic malignancies.
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PMID:Cytogenetic analysis of hematologic malignancies in Hong Kong. A study of 98 cases. 139 2

A case of isolated thrombocytopenia with decreased platelet production and abnormal megakaryopoiesis is described. In the bone marrow, a chromosomally aberrant clone, 45,XX,-11,-18,+der (11;18)(11q13;18p11), was found. These findings indicate a myelodysplastic nature of the abnormal thrombocytopoiesis. The described case demonstrates the value of a bone marrow examination including histopathology with immunologic techniques to evaluate the megakaryopoiesis in thrombocytopenia and the interest of cytogenetic studies not only in instances with overt hematologic malignancies or complete myelodysplastic syndromes, but also when morphologic abnormalities occur in a single cell line.
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PMID:Dysplastic megakaryopoiesis with thrombocytopenia and chromosomal aberration. 151 34

A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.
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PMID:Vasculitis associated with malignancy. 154 62

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC-mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC-mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.
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PMID:Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies. 171 80

The myelodysplastic syndromes are acquired clonal hematologic malignancies characterized by progressive cytopenia and an increased risk of evolution to acute myeloid leukemia. It mainly affects elderly people, but may also be found in younger patients and children. MDS represents a heterogeneous group of disorders. Some patients will experience prolonged survival, whereas a substantial number of patients will die within the first year after diagnosis. Treatment of patients should be based on life expectancy. Patients with pancytopenia, excess of bone marrow blasts, complex chromosome abnormalities, abnormal chromosome 7, older age and secondary MDS have a poor prognosis. Several simple scoring systems are available, based on peripheral counts, percent of bone marrow blasts and age, that provide significant prognostic information about life expectancy in patients with MDS. The most widely used is the Bournemouth scoring system. The prognostic factors and the scoring systems are reviewed.
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PMID:Prognostic factors in the myelodysplastic syndromes. 173 63

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

The activity of microsomal HMG-CoA reductase in freshly isolated leukocytes from patients with a variety of hematologic malignancies was significantly increased (up to 20-fold) when compared to enzyme activity in leukocytes from normal subjects (average 10.3 +/- 0.8 pmol/min per mg). Increased enzyme activity was not due to nonspecific leukocyte stimulation or to the presence of a malignancy, since normal enzyme activity was observed in subjects with either viral illnesses or solid tumors. Increased HMG-CoA reductase activity accompanying hematologic malignancy could also not be attributed to alterations in enzyme-substrate kinetic parameters (Km), or to alterations in the phosphorylation state or thiol-disulfide status of the enzyme, nor was it correlated with differences in serum lipid or lipoprotein concentrations. The increase (3.6-fold) in HMG-CoA reductase activity in leukocytes from patients with preleukemia was due entirely to a rise in enzyme catalytic efficiency (specific activity), whereas the increase (4.3-fold) observed in leukocytes from patients with overt leukemia or non-Hodgkin's lymphoma was due to a concomitant increase in both enzyme catalytic efficiency (2.5-fold) and enzyme protein concentration (1.6-fold). Similar increases in HMG-CoA reductase activity and catalytic efficiency were also noted for both transformed, nonmalignant, and malignant cultured leukocytes, suggesting that increased enzyme catalytic efficiency is not a nonspecific consequence of physiological changes occurring in response to the malignancy but may be an integral aspect of the malignant phenotype. HMG-CoA reductase protein concentrations, however, were not elevated in either transformed, nonmalignant, or malignant cultured leukocytes, suggesting that increases in enzyme protein levels may be secondary to other physiological changes that occur during the development of overt leukemia. Taken together, these observations suggest that an increase in the activity of HMG-CoA reductase, the rate-controlling enzyme in cholesterol synthesis, is a common occurrence in human hematologic malignancies and that a biphasic elevation of enzyme activity may exist in malignant leukocytes, such that changes in catalytic activity may occur early in tumorigenesis and may be followed by secondary changes in enzyme levels.
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PMID:In vivo regulation of human leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase: increased enzyme protein concentration and catalytic efficiency in human leukemia and lymphoma. 177 Mar 7

We report 2 of 80 cases of myelodysplastic syndromes (MDS) cytogenetically studied, with involvement of chromosome 13. The first case had a t(6;13), and the second had a t(1;13). Abnormalities of chromosome 13 mainly involving loss of band 13q14 have been described in hematologic malignancies. In both our cases band 13q14 did not participate in the deleted segment.
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PMID:Involvement of chromosome 13 in myelodysplastic syndromes. 193 15

Indirect immunofluorescence staining with monoclonal antibody (MoAb) CL203.4 of malignant cells from 269 patients with hematologic malignancies showed a heterogeneous expression of CD54/intercellular adhesion molecule-1 (ICAM-1). This marker was expressed by malignant cells of 57 out of 118 patients with myeloid malignancies and 69 out of 135 with B-lymphoid malignancies. On the other hand, CD54 was not detected on malignant cells of 16 patients with T-lymphoid malignancies. In myeloid malignancies, CD54 is preferentially expressed by "stem cell-derived" malignancies, being detectable on blast cells from almost all patients affected by chronic myelogenous leukemia in blast phase or myelodysplastic syndromes and by only 34% of patients with de novo acute myeloid leukemia (AML). The expression of CD54 did not correlate with any specific myeloid FAB subtype, although three cases of highly undifferentiated AML (FAB MO) displayed maximal levels of the antigen. The expression of CD54 in AML was significantly associated with that of CD34 and HLA-DR antigens. In B-lymphoid malignancies, CD54 expression appears to correlate with the differentiation stage of malignant cells, since B-origin acute lymphoblastic leukemias and conventional B-chronic lymphocytic leukemias (B-CLL; ie, "dim SIg" CLL) expressed lower levels of CD54 than more mature lymphoproliferative disorders ("bright SIg" CLL, prolymphocytic leukemias, and lymphoplasmacytic tumors). "High-grade" B-cell non-Hodgkin's lymphomas (B-NHL) express in general a higher level of CD54 than "low-grade" ones. This finding in conjunction with the expression of CD54 in all 17 patients with "bright SIg" CLL investigated (characterized by marked organomegaly and poor prognosis) suggest that the differential expression of CD54 in lymphoproliferative disorders may also relate to their degree of malignancy.
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PMID:Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders. 197 71


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