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)

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 gene coding for Zn-alpha 2-glycoprotein (AZGP1), a human protein with a high degree of similarity to class I major histocompatibility complex (MHC) antigens, was mapped by fluorescent in situ hybridization to chromosome 7q22, a common breakpoint in myelodysplastic syndromes. Since classical MHC genes map on chromosome 6, this assignment indicates that besides duplication of the putative common ancestor gene, transposition events to different chromosomes have also been involved in the evolutionary diversification of this gene family.
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PMID:Mapping of the human Zn-alpha 2-glycoprotein gene (AZGP1) to chromosome 7q22 by in situ hybridization. 816 3

The combination of flow cytometric scatterplot analysis and specific monoclonal antibodies was used to evaluate the lineage of cells from six dogs with proliferative disorders of bone marrow. Scatterplot analysis was used to identify mature and immature myeloid and erythroid cells. The immunophenotype of cells in the immature myeloid gate was determined by labeling cells with four monoclonal antibodies. These results were compared to results of cytologic and cytochemical evaluation. The immunophenotype of a dog with a diagnosis of myelogenous leukemia was a cluster of differentiation-18 (CD-18) positive, CD-14 negative, Thy-1 negative, and a major histocompatibility complex (MHC) class II negative. The immunophenotype of a dog with a diagnosis of myelomonocytic leukemia was CD-18 positive, CD-14 positive, Thy-1 positive, and MHC class II positive. Although this phenotype clearly differentiated myelomonocytic leukemia from myelogenous leukemia, it was similar to the immunophenotype of dogs with a diagnosis of malignant histiocytosis or hemophagocytic syndrome. The immunophenotype of two dogs with myelodysplastic syndrome was CD-18 positive and CD-14 negative. Results for Thy-1 and MHC class II were variable. As additional lineage-specific monoclonal antibodies become available, immunophenotyping should become a valuable tool for determination of the lineage of cells in canine myeloproliferative disorders.
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PMID:Evaluation of proliferative disorders in canine bone marrow by use of flow cytometric scatter plots and monoclonal antibodies. 1157 58

Clinical observations and experimental evidence link bone marrow failure in myelodysplastic syndrome (MDS) with a T cell-dominated autoimmune process. Immunosuppressive therapy is effective in improving cytopenias in selected patients. Trisomy 8 is a frequent cytogenetic abnormality in bone marrow cells in patients with MDS, and its presence has been associated anecdotally with good response to immunotherapy. We studied 34 patients with trisomy 8 in bone marrow cells, some of whom were undergoing treatment with antithymocyte globulin (ATG). All had significant CD8+ T-cell expansions of one or more T-cell receptor (TCR) Vbeta subfamilies, as measured by flow cytometry; expanded subfamilies showed CDR3 skewing by spectratyping. Sorted T cells of the expanded Vbeta subfamilies, but not of the remaining subfamilies, inhibited trisomy 8 cell growth in short-term hematopoietic culture. The negative effects of Vbeta-expanded T cells were inhibited by major histocompatibility complex (MHC) class 1 monoclonal antibody (mAb) and Fas antagonist and required direct cell-to-cell contact. Sixty-seven percent of patients who had de novo MDS with trisomy 8 as the sole karyotypic abnormality responded to ATG with durable reversal of cytopenias and restoration of transfusion independence, with stable increase in the proportion of trisomy 8 bone marrow cells and normalization of the T-cell repertoire. An increased number of T cells with apparent specificity for trisomy 8 cells is consistent with an autoimmune pathophysiology in trisomy 8 MDS.
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PMID:Preferential suppression of trisomy 8 compared with normal hematopoietic cell growth by autologous lymphocytes in patients with trisomy 8 myelodysplastic syndrome. 2733 45

Human leukocyte antigen G (HLA-G) molecules exhibit immunomodulatory properties corresponding to nonclassic class I genes of the major histocompatibility complex. They are either membrane-bound or solubly expressed during certain tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G) molecules seem more frequently expressed than membrane-bound isoforms during hematologic malignancies, such as lymphoproliferative disorders. Assay of these molecules by enzyme-linked immunosorbent assay in patients suffering from another hematologic disorder (acute leukemia) highlights increased sHLA-G secretion. This increased secretion seems more marked in acute leukemia subtypes affecting monocytic and lymphoid lineages such as FABM4 and FABM5, as well as both B and T acute lymphoblastic leukemia (ALL). Moreover, this study uses in vitro cytokine stimulations and reveals the respective potential roles of granulocyte-macrophage colony-stimulating factor and interferon-gamma in increasing this secretion in FABM4 and ALL. Correlations between sHLA-G plasma level and clinical biologic features suggest a link between elevated sHLA-G level and 1) the absence of anterior myelodysplasia and 2) high-level leukocytosis. All these findings suggest that sHLA-G molecules could be a factor in tumoral escape from immune survey during acute leukemia.
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PMID:Soluble HLA-G molecules increase during acute leukemia, especially in subtypes affecting monocytic and lymphoid lineages. 1661 16

Mesenchymal stem cells (MSC) are multipotential nonhematopoietic progenitor cells capable of differentiating into multiple mesenchymal tissues. MSC are able to reconstitute the functional human hematopoietic microenvironment and promote engraftment of hematopoietic stem cells. MSC constitutively express low levels of major histocompatibility complex-I molecules and do not express costimulatory molecules such as CD80, CD86 or CD40, thus lacking immunogenicity. Furthermore, they are able to suppress T- and B-lymphocyte activation and proliferation and may also affect dendritic cell maturation. Based on these properties, MSC are being used in regenerative medicine and also for the treatment of autoimmune diseases and graft-versus-host disease. On the other hand, MSC from patients diagnosed with myelodysplastic syndromes or multiple myeloma display abnormalities, which could play a role in the physiopathology of the disease. Finally, in patients with immune thrombocytopenic purpura, MSC have a reduced proliferative capacity and a lower inhibitory effect on T-cell proliferation compared with MSC from healthy donors.
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PMID:Immunomodulatory effect of mesenchymal stem cells. 2049 Apr 29