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)

The expression of the MDR1 gene, a multidrug resistance gene, was determined in patients (N = 24) with myelodysplastic syndrome or acute myeloid leukemia evolving from it. MDR1 RNA expression of the mononuclear cells was detected in 14 (58%) patients. Among patients who had progressed to acute myeloid leukemia (sAML) (N = 14), MDR1 RNA expression was seen in 8 (57%) patients. Expression was observed in the 2 patients who had been pretreated with MDR drugs. These findings indicate that the MDR1 gene is frequently expressed in MDS or sAML and suggest that multidrug resistance might be involved in the clinical drug resistance of these diseases.
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PMID:MDR1 gene expression in myelodysplastic syndrome and in acute myeloid leukemia evolving from myelodysplastic syndrome. 791 92

The expression of the multidrug resistance (MDR-1) gene product, P-170 glycoprotein (P-170) was investigated in 26 patients with low-risk (n = 9) or high-risk (n = 17) myelodysplastic syndrome (MDS), using a panel of monoclonal antibodies to P-170 (C219, JSB1, C494, MRK16) and quantitative analysis of MDR-1 mRNA. P-170 membrane staining was demonstrated in bone marrow blast cells of 14/17 HR-MDS and in 2/9 LR-MDS patients (p < 0.01). P-170 expression was associated with the presence of blast cells characterized by an immature or early myeloid phenotype as defined by CD34 expression (p = 0.034), CD13 or CD33 expression (p = 0.0006), or CD13/33 plus terminal deoxynucleotidyl transferase (TdT) double expression (p = 0.04). With double fluorescence analysis, P-170 expression was observed in a subset of CD34+ cells, but not in CD34- cells. P-170 expression was present in 13/15 (86%) patient samples with an abnormal karyotype as compared with 3/10 samples (30%) with a normal karyotype (p < 0.05). Nine of these 15 patients had a loss or a deletion of chromosome 7. Thirteen out of 16 (81%) MDR-1 positive patients developed acute leukemia versus two of ten (20%) MDR-1 negative patients (p = 0.025). It is concluded that MDR-1 expression in MDS is present in cells with an immature phenotype and is frequently observed in patients who have an abnormal karyotype and a high risk of leukemic transformation.
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PMID:High expression of the multidrug resistance P-glycoprotein in high-risk myelodysplasia is associated with immature phenotype. 810 Jun 4

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.
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PMID:Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis. 862 74

The genes for acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) are located within regions subject to non-random chromosomal abnormalities in the myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Acetylcholinesterase is mapped to 7q22, within the critical deleted region presumed to contain a myeloid specific tumour suppressor gene. Butyrylcholinesterase is mapped to 3q26: abnormalities at this region are associated with sub-types of MDS and AML with thrombocytopenia, or with increased platelet counts. Both ACHE and BCHE have been implicated as playing a role in megakaryopoiesis and thrombopoiesis, and these genes have been observed to be co-amplified in acute myeloid leukaemia. Recent findings suggest a more significant role for the ACHE gene in haemopoiesis by regulating multipotent stem cell proliferation, and apoptosis in cells undergoing erythroid and myeloid differentiation. This led us to investigate gene copy-number alterations at these genes in MDS and AML. Samples were screened by slot-blot hybridization, and if changes were observed, by Southern blotting. A total of 42 samples from 31 de novo AML patients, 10 samples from eight cases of post-MDS AML and 85 samples from 67 MDS patients were analysed with probes for ACHE, BCHE, c-MYC, MDR-1 and globin control. Changes in ACHE and/or BCHE were observed in 9/31 de novo AML patients, and in 7/67 MDS patients: 1/37 cases of refractory anaemia (RA), 1/10 cases of refractory anaemia with excess blasts (RAEB) and 5/20 chronic myelomonocytic leukaemia (CMML) patients. The amplification events observed generated copy numbers no greater than 10, showed normal restriction patterns and had no clear correlation with megakaryopoiesis or thrombopoiesis. Loss of signal at the ACHE locus was observed: haploid signal intensity was seen in seven samples: one RA with thrombocytopenia, three CMML, one AML-M5a (no karyotypic abnormalities of chromosome 7), one AML-M4 (monosomy 7), and one case of AML-M7 (karyotype unknown). Homozygous deletion was observed at relapse of an additional patient with AML-M4. These data reinforce the possibility that ACHE may play a role as a myeloid tumour suppressor gene.
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PMID:Deletion of the acetylcholinesterase locus at 7q22 associated with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). 863 18

Expression of P-glycoprotein (PGP), the product of the multidrug resistance gene (mdr1), is common in myelodysplastic syndromes (MDSs) and explains in part the low rate of complete remissions (CRs) obtained after aggressive chemotherapy. Reversion of the mdr phenotype to restore chemosensitivity has been the focus of many studies over the last ten years. Two phase III studies evaluated quinine for obtaining reversion of mdr gene expression in MDSs treated by aggressive chemotherapy. Results suggested better response rates and longer survival times in quinine-treated MDR-positive patients. However, the toxicity of quinine warrants further work aimed at developing other mdr phenotype reversion-inducing agents. Some such agents have proved superior over quinine in in vitro studies. Reversion of other mechanisms underlying chemoresistance in MDSs is a promising avenue of research.
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PMID:[Multi-drug resistance and myelodysplastic syndromes: a possible role for remission inducing agents?]. 956 29

The purpose of this investigation was to explore the expression of nm23-H(1) gene in patients with myelodysplastic syndrome (MDS) and evaluate the relationship between nm23-H(1) expression and therapeutic outcomes. Semi-quantitative RT-PCR was used to detect the expression of nm23-H(1) mRNA in marrow mononuclear cells from 28 MDS patients and 15 normal subjects. nm23-H(1)/GAPDH ratio >/= 0.5 was believed to a positive case. The expression of nm23-H(1) was positive in 24 of 28 MDS patients, and the average level was 0.89 +/- 0.56. nm23-H(1) mRNA was negative in normal controls. The overexpression of nm23-H(1) mRNA in MDS patients could predict outcome of treatment and prognosis for MDR patients.
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PMID:[Expression of nm23-H(1) mRNA in Bone Marrow Cells from Patients with Myelodysplastic Syndrome and Its Clinical Implication] 1257 33

Seventy to 80% of patients with acute myeloid leukemia (AML) achieve complete remission (CR) by chemotherapy, but more than 50% of them then relapse. Phase III clinical trials in the treatment of patients with previously untreated AML and acute promyelocytic leukemia (APL) are ongoing in Japan (JALSG AML 201, APL 204). And continuous efforts are being made to improve the efficacy of chemotherapy. We discussed six topics in the treatment of AML. (1) To determine whether adding the MDR-1 modulator to chemotherapy provided clinical benefits to patients with AML and high-risk myelodysplastic syndrome (MDS), a phase III randomized study was performed using PSC 833. CR rates and overall survival (OS) were not improved by using PSC 833 compared to chemotherapy alone. (2) A large randomized study selectively focused on the G-CSF priming was performed. Among patients in this study attaining CR, the probability of relapse was reduced when they had been assigned to treatment with G-CSF along with induction chemotherapy. The benefit of chemotherapy-sensitization by G-CSF was particularly evident among the intermediate-risk. (3) Fludarabine in addition to Ara-C increases the accumulation of Ara-CTP, which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase III trial, patients with high-risk MDS or patients with AML were randomized to receive 2 induction courses consisting of Ara-C and G-CSF during and after chemotherapy with or without fludarabine (FLAG versus AG). Although Ara-CTP accumulation in leukemic cells after FLAG was enhanced, the clinical outcome in terms of CR rate, OS, event-free survival, and disease-free survival was not significantly improved by combining fludarabine with Ara-C. (4) Calicheamicin-conjugated humanized anti-CD 33 mouse monoclonal antibody, mylotarg, has recently been introduced. In combined phase II studies of 277 patients with CD 33-positive AML in their first relapse, the overall response rate was 26%. (5) Arsenic trioxide (ATO) has been established as a highly effective therapy for patients with APL, even for those with disease refractory to ATRA. ATO was recently approved in Japan. (6) There has been great interest in developing FLT 3 inhibitors because of the high frequency and poor prognosis of AML patients with mutant FLT 3. Some compounds are currently under development.
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PMID:[Current and new therapeutic strategies in acute myeloid leukemia]. 1579 11

MDR Pseudomonas aeruginosa strains are isolated from clinical specimens with increasing frequency. It seems that acquiring genes which determine antibiotic resistance usually comes at a biological cost of impaired bacterial physiology. There is no information on investigations comparing phenotypic differences in MDR and MDS P. aeruginosa strains in literature. The study included 150 clinical P. aeruginosa isolates (75 classified as MDS and 75 as MDR). PFGE analysis revealed five pairs of identical isolates in the group of MDR strains and the results obtained for these strains were not included in the statistical analyses. MDR strains adhered to polystyrene to a lesser extent than MDS strains. The growth rate in the liquid medium was significantly lower for MDR strains. Detectable amounts of alginate were present in the culture supernatants of seven MDS and six MDR strains. The MDR P. aeruginosa strains which were investigated produced significantly lower amounts of extracellular material binding Congo Red, lower lipolytic, elastase, LasA protease, phospholipase C activity and pyocyanin quantity in culture supernatants when compared with MDS strains. No significant differences were observed between MDR and MDS strains in proteolytic activity. In conclusion, the MDR P. aeruginosa strains have impaired virulence when compared to MDS strains.
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PMID:Reduced expression of virulence factors in multidrug-resistant Pseudomonas aeruginosa strains. 1996 Mar 37

We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.
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PMID:Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study. 2121 91

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by abnormal hematopoietic differentiation and maturation, which progress toward acute leukemia in approximately 30% of the cases. Drug metabolism polymorphisms in Cytochrome P450 2B6 (CYP2B6), Glutathione S-transferase (GST) and Dehydrogenase Quinone 1 (NQO1) enzymes and P-glycoprotein (MDR-1) could modify enzyme activity. Thus, the aim of this study was to identify the influence of CYP2B6 G15631T, GSTT1, GSTM1, NQO1 C609T and MDR-1 C3435T polymorphisms on MDS progression. We analyzed 78 MDS patients using the PCR-RFLP and multiplex method. The frequency of GST deletions and MDR-1 CC genotype was lower in progression-free patients compared to patients with progression; GST: 17% vs. 35% (P=0.018); MDR-1 gene: 19% vs. 48% (P=0.012). We also verified the influence of GST deletions and MDR-1 C3435T on patient overall survival and found no significant difference (RR=0.75; P=0.599 and RR=0.79; P=0.594 respectively). We concluded that GSTM1 deletion may contribute toward MDS progression probably due to toxic metabolite accumulation which generates cell toxicity and DNA damage. Moreover, MDR-1 C3435T may have a protective effect against MDS progression because the expected lower expression of P-glycoprotein would lead to a higher degree of cell death. To the best of our knowledge, this is the first study showing the relationship of these polymorphisms with MDS progression.
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PMID:MDR-1 and GST polymorphisms are involved in myelodysplasia progression. 2385 17


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