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)

Thirty-five patients, 24 males and 11 females, with myelodysplastic syndromes were studied for the expression of c-myc encoded p67 oncoprotein. According to FAB classification, 5 patients had refractory anaemia (RA). 5 refractory anaemia with ringed sideroblasts (RARS), 17 refractory anaemia with excess of blasts (RAEB), 4 refractory anaemia with excess of blasts in transformation (RAEB-t), and 4 chronic myelomonocytic leukaemia (CMML). The mouse anti-human 9E10 derived monoclonal antibody in the standard APAAP technique for immunohistochemical analysis was used. A scoring method similar to that routinely used for endogenous neutrophil alkaline phosphatase estimation, was applied to obtain parametrically comparable results. In all but two MDS patients, the observed c-myc oncoprotein score values did not differ statistically from those found in the controls. The values did not correlate with peripheral blood or bone marrow blast cell numbers. In two out of 17 patients with RAEB in whom very high c-myc score values were found, acute non-lymphocytic leukaemia (ANLL) was diagnosed 30 and 45 days later, respectively. Furthermore, we found high c-myc score values in three patients with RAEB and in two patients with RAEB-t during the ANLL phase which was diagnosed six to ten months after the initial study. Our data suggest that c-myc activation may be seen in all cases of MDS in overt ANLL phase, and also in some RAEB patients a few weeks before diagnosis of overt ANLL. The possible prognostic value of c-myc activation in MDS patients remains to be clarified.
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PMID:Increased expression of c-myc p67 oncoprotein in patients with myelodysplastic syndromes in transformation to acute leukaemia. 928 97

Disease recurrence following successful bone marrow transplantation remains a major impediment in the management of patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A variety of monoclonal antibodies that deliver drugs or toxins to the site of activity, have been used in an attempt to augment marrow transplantation. Examples of three different monoclonal antibody techniques (naked antibody, drug antibody conjugations, and radiolabeled antibodies) are discussed. CD33 is an attractive antigen to use as a target for treating AML because it is present on most AML cells. Naked antibodies are limited in their ability to kill tumor cells, although studies to date suggest there may be a role in antileukemic therapy for unlabeled anti-CD33 humanized M195 antibody after the tumor burden has been reduced by chemotherapy. Calicheamicin, a novel and toxic drug moiety conjugated to anti-CD33 antibody, is currently under investigation in patients with refractory or relapsed AML. Results from a Phase I investigation were encouraging. Three different radiolabeled monoclonal antibodies have been evaluated in Phase I/II studies--131I-labeled anti-CD33 (p67) antibody, 213Bi-labeled humanized M195 antibody, and 131I-anti-CD45 antibody. CD45 is a cell-surface antigen broadly expressed by all circulating leukocytes and lymphocytes. Initial studies demonstrated that substantially greater doses of radiation could be delivered to targeted organs compared with nontargeted organs using 131I-anti-CD45 antibody. This approach offers the potential for augmenting leukemia therapy without increased risk of toxicity.
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PMID:Immunotherapy in acute myelogenous leukemia and myelodysplastic syndrome. 977 93

Recent progress in understanding the pathobiology of the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have led to the development of various immunologically oriented therapies for these diseases. The existence of elevated levels of tumor necrosis factor-alpha (TNF-alpha) in bone marrow during early stages of MDS, and the possibility that TNF- proportional, variant suppresses normal hematopoiesis led to studies of attempts to block the activity of TNF-alpha. An anti-TNF monoclonal antibody and an antibody comprised of the soluble extracellular ligand-binding portion of the TNF receptor have both been evaluated recently in several small pilot studies. The recognition that marrow suppression in MDS may, in part, be a T-cell mediated autoimmune process has stimulated various trials of antithymocyte globulin and other similar agents. Gemtuzumab ozogamicin, an antibody against CD33 conjugated to the cytotoxic agent calicheamicin, is approved for use in AML and is currently being investigated as a potential therapeutic agent in MDS. Clinical trials were conducted as either monotherapy or in combination with cytokines such as IL-11 and chemotherapeutic agents including idarubicin, fludarabine, and/or cytarabine. Other antibodies are being developed as immunoconjugates with radioisotopes as part of conditioning regimens prior to bone marrow transplantation for AML or MDS. These include (131)I-anti-CD45 antibody (BC8), (131)I anti-CD33 antibody (p67), (213)Bi-M195 antibody, and (188)Re-labeled anti-CD66 antibody. The clearest example of successful immunotherapy for MDS (and AML) is the use of the graft-versus-tumor effect associated with allogeneic hematopoietic cell transplantation. Recently, nonmyeloablative transplants have been explored with encouraging results. Vaccines using overexposed self-antigens such as WT1 and PR1 are other attempts to induce a T-cell mediated response against MDS.
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PMID:Immunobiologic therapies for myelodysplastic syndrome. 1549 1