Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efficacious lentiviral vaccines designed to induce cytotoxic T lymphocytes (CTL) in outbred populations with a diverse repertoire of MHC class I molecules should contain or express multiple viral proteins. To determine the equine infectious anaemia virus (EIAV) proteins with epitopes most frequently recognized by CTL from seven horses infected for 0.5 to 7 years, retroviral vector-transduced target cells expressing viral proteins were used in CTL assays. Gag p15 was recognized by CTL from 100% of these infected horses. p26 was recognized by CTL from 86%, SU and the middle third of Pol protein were each recognized by 43%, TM by 29%, and S2 by 14%. Based on these results, it is likely that a construct expressing the 359 amino acids constituting p15 and p26 would contain epitopes capable of stimulating CTL in most horses.
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PMID:Equine infectious anaemia virus proteins with epitopes most frequently recognized by cytotoxic T lymphocytes from infected horses. 1103 86

We report herein a 38-year-old male patient with Fanconi anemia but with few phenotypic manifestations--short stature, sterility, and hypoplasic anemia with several years of evolution-who developed a myelodysplastic syndrome (MDS). Bone marrow karyotype showed long arm triplication of chromosome 1 (q12-21q31-q32), and two markers add(11)(p15) and add(21)(q22) which had extra material of chromosome 3 besides the normal chromosome 3 pair. Peripheral blood showed chromosome instability; SCE was normal. Both the patient and his family showed a high prevalence of malignant diseases. 1q duplication and, in a few cases, triplication of 1q has been related to Fanconi anemia, being of unknown significance.
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PMID:Triplication of 1q in Fanconi anemia. 1140 63

5-Azacytidine, a DNA methyl transferase inhibitor, is effective in patients with myelodysplastic syndromes (MDS). Whether responses to 5-Azacytidine are achieved by demethylation of key genes or by cytotoxicity is unclear. Of 34 patients with MDS or acute myeloid leukaemia (AML) treated with 5-Azacytidine, 7 achieved complete remissions (CR) (21%) and 6 achieved haematological improvement. All six had less than 5% bone marrow (BM) blasts at the time of haematological improvements (HI) (2 had pre-existing refractory anaemia (RA), 4 had refractory anaemia with excess blasts (RAEB)). A further patient with RAEB had blast reduction to less than 5% without HI. Five of the seven (71%) complete responders had chromosome 7 abnormalities. BM CR predicted longer overall survival (OS) (median 23 versus 9 months, P=0.015). Bisulphite genomic sequencing (BGS) of the CDKN2B (p15(INK4b)) promoter showed low level, heterogeneous pretreatment methylation (mean 12.2%) in 14/17 (82%) patients analysed. Lower baseline methylation occurred in responders (9.8% versus 16.2% in non-responders P=0.07). No response was seen in patients with >24% methylation, in whom p15(INK4b) mRNA was not expressed. 5-Azacytidine reduced CDKN2B methylation by mean 6.8% in 8/17 (47%) patients, but this did not correlate with response. At 75 mg/m(2), cell death (reduced BM cellularity (P=0.001) and increased apoptosis (P=0.02)) rather than demethylation of CDKN2B correlates with response. Patients with >24% methylation may benefit from alternative dosing or combination strategies.
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PMID:CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine. 1761 69

Most patients with myelodysplastic syndrome (MDS) are classified at diagnosis as having a low/INT-I or INT-II/high risk disease, based on the classical International Prognostic Scoring System (IPSS) criteria. The low/INT-I risk patients are usually managed mildly with supportive care, including red blood cell (RBC) transfusions, erythroid stimulating agents (ESAs), other cytokines (G-CSF, platelet stimulating agents), as well as thalidomide and lenalidomide. Some patients receive immunosuppressive therapy, and iron chelation is indicated in iron overloaded patients. Aggressive approach (hypomethylating agents, chemotherapy and stem cell transplantation) is usually not applied in such patients. Occasionally, we observe a "low risk" patient with rapid progression of disease and poor outcome. Can we identify demographic, clinical, laboratory, cellular-biological and/or molecular parameters that can predict "poor prognostic features" (PPF) in "low risk" MDS patients? Clinical and laboratory parameters have been reported to be associated with poor prognosis, in addition to the known "classical" IPSS criteria. These include older age, male gender, poor performance status, co-morbidities, degree of anemia, low absolute neutrophile count (ANC) and platelet counts, RBC transfusion requirements, high serum ferritin, high LDH, bone marrow (BM) fibrosis, increased number of BM CD34+ cells and multi-lineage dysplasia. Certain immunophenotypes (low CD11b, high HLA-Dr, CD34, CD13 and CD45), clonal granulocytes, multiple chromosomal abnormalities, chromosomal instability, short telomeres and high telomerase activity were also reported as PPF. Studies of apoptosis identified Bcl-2 expression and high caspase 3 as PPF, while the reports on survivin expression have been confusing. Recent exciting data suggest that methylation of p15 INK4b and of CTNNA1 (in 5q-), high level of methylation of other genes, absence of the TET2 mutation, down regulation of the lymphoid enhancer binding factor 1 (LEF1), mutation of the polycomb-associated gene ASXL1 and a specific 6-gene signature in gene expression profiling - are all associated with poor prognosis in MDS. Do we have data suggesting a different treatment for "low risk" MDS patients displaying PPF? Two teams, the combined Nordic-Italian and the GFM groups have reported an improved survival with ESAs. The GFM has achieved prolonged survival with iron chelation. Recently, encouraging data with survival advantage in azacitidine-treated patients have been published, including a few INT-I patients. Finally, data suggest that low/INT-I MDS patients who undergo stem cell transplantation (SCT0 do better than INT-II/high risk patients). In summary, some patients, classified as "low risk MDS" carry PPF. An appropriate therapeutic approach is indicated. Future updated classifications and prospective trials may lead to a better outcome.
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PMID:The lower risk MDS patient at risk of rapid progression. 2057 98


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