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 ras proto-oncogenes encode membrane bound proteins (p21) which are structurally distinct from the proteins encoded by the activated transforming ras genes. These activated ras genes have been identified in various human tumors as well as their preneoplastic lesions such as colorectal tumors (20-40%), pancreatic carcinomas (95%), lung carcinomas (20-30%), myelodysplasia (40%) and acute myeloid leukemia (30%). The activation of ras p21 is due to amino acid substitutions at positions 12, 13 or 61 of the p21 protein. This report describes two monoclonal antibodies designated D129 and D146 raised against a synthetic peptide corresponding to amino acids 5-16 of ras p21 activated by the substitution of aspartic acid for glycine at position 13. D129 and D146 react specifically with the peptide with the aspartic acid substitution at position 13, but not with the peptide with valine at position 13 or the peptide containing the normal glycine at position 13. Western blot analysis demonstrates that D129 and D146 react specifically with p21 extracted from transformed NIH3T3 fibroblast lines containing aspartic acid at position 13. These studies also demonstrate that D146 is able to detect the activated p21 with aspartic acid at position 13 that is shed into the culture media. Studies demonstrate that MAb D146 specifically immunoprecipitates the cellular p21 with aspartic acid at position 13 from transformed NIH3T3 cells, whereas D129 cannot immunoprecipitate the activated p21. Using a sandwich ELISA format, D146 is able to detect the p21 with position 13 aspartic acid from cell extracts and culture fluids. The ability of D146 to function in the ELISA format raises the possibility that this assay maybe a quick and effective way of determining the presence of activated p21 with aspartic acid at position 13 in human fluids and tissues.
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PMID:Characterization of monoclonal antibodies specific to the activated ras p21 with aspartic acid at position 13. 220 49

The aim oof this study was to investigate the immunohistochemical expression of p53, mdm2, and waf1/p21 proteins in myelodysplastic syndromes (MDS), acute myelogenous leukaemias (AML), and chronic myeloproliferative disorders (CMPD). Paraffin-sections of bone marrow biopsies from 30 cases of MDS (6 cases of RAEB and RAEB-T) 22 AML (4 cases occurring in the setting of MDS), 16 chronic myeloproliferative disorders (CMPD), and 10 cases without alterations were investigated by immunohistochemistry for p53, waf1/p21, mdm2 and Ki67 proteins. P53 was detected in immature myeloid cells in 6/30 MDS (20%) and in 6/22 AML (27%) while it was not expressed in CMPD. Of the 6 p53 positive AML, 3 occurred as evolution of MDS and 3 were de novo acute leukaemias. Waf1/p21 was detected in 5/22 (23%) AML in immature myeloid cells. Waf1/p21 was also expressed in 18/30 (60%) MDS and 10/16 (63%) CMPD in variable proportion (5-25%) of the mature myeloid cells and megakaryocytes. Waf1/p21 was not detected in immature myeloid cells in MDS and CMPD. Mdm2 protein was expressed in 3/30 (10%) MDS in the immature myeloid cells and in 1/22 AML in blastic cells. The combined immunophenotypes of immature myeloid cells of MDS were: p53+/mdm2+/waf1-: 3, p53+/mdm2-/waf1-: 3, while the immunohistochemical patterns of AML were: p53+/mdm2-/waf1-: 4, p53+/mdm2+/waf1+: 1, p53+/mdm2-/waf1+: 1, p53-/mdm2-/waf1+: 3. Ki67/MIB1 staining was found in at least 30% of immature myeloid cells in MDS and AML and in at least 20% of these cells in CMPD. In conclusion, our results indicate that p53 protein is overexpressed in the myeloid lineage in a proportion of AML and MDS, while is not detected in CMPD and normal bone marrow, p53 expression was much more frequent in AML occurring as an evolution of MDS than in de novo AML. The combined immunophenotypes of p53 positive AML and MDS suggest that p53 overexpression may be due to mutation, in some AML and MDS cases with the p53+/mdm2-/waf1- phenotype. However, it would be also possible that p53 protein accumulation is not related to p53 mutation but to inhibition of p53/mdm2 binding due to mdm2 defects and/or other events related to cell stress signals. On the other hand, waf1/p21 protein overexpression without p53 expression in some AML could be p53-independent and may represent an attempt to control the high proliferation rate which was evidenced by Ki67/MIB1 immunostaining. However, the possibility of p21 to arrest cell-cycle, in these cases of AML, seems to be overridden, suggesting that cell-cycle deregulation may be involved in a proportion of AML.
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PMID:Immunohistochemical detection of p53, mdm2, waf1/p21, and Ki67 proteins in bone marrow biopsies in myelodysplastic syndroms, acute myelogenous leukaemias and chronic myeloproliferative disorders. 1059 72

p53 together with its downstream product p21 plays an important role in tumorigenesis development. MDM2 and MDM4 are two p53 regulators. We studied the expression of p53, p21, MDM2, and MDM4 in a total of 120 cases of myeloid neoplasms including MDS, AML or MDS/MPN, and control, using single and double immunohistochemical stains. We found TP53 mutations had a worse outcome in patients with AML/MDS, and p53 expression detected by immunohistochemistry had a similar prognostic value. p21 expression was strongly related to TP53 mutation status, with loss of expression in almost all TP53 mutated cases. MDM2 and MDM4 were highly expressed in hematopoietic cells in both benign and neoplastic cells. MDM2/p53 double positive cells exceeded MDM4/p53 double positive cells in neoplastic cases. Finally, we observed that p21 protein expression was up regulated upon the use of ALRN-6924 (Aileron) while no significant changes were seen in p53, MDM2 and MDM4 expression.
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PMID:The expression of MDM2, MDM4, p53 and p21 in myeloid neoplasms and the effect of MDM2/MDM4 dual inhibitor. 3292 82