Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 68 year old female who presented with long-term thrombocytopenia was clinically diagnosed as having chronic idiopathic thrombocytopenia purpura (ITP). Increased levels of the tumour suppressor p53 protein were detected by immunohistochemistry in the neutrophils and some monocytes of the peripheral blood preparation using the antibody DO-1, recognizing mutant and wild type p53 protein conformations. However, no positive staining in the peripheral blood samples from 41 myelodysplasias (MDS) and six normal individuals was observed. Single-stranded conformational polymorphism analysis performed on DNA extracted from the cytospin preparations from this patient indicated no mutations in exons 5-8 of the p53 gene. This report describes the unusual detection of elevated p53 protein in a non-neoplastic condition by immunohistochemistry using the antibody DO-1. This unexpected finding raises the possibility of classifying such patients as early MDS on the basis of their p53 status.
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PMID:Elevated levels of p53 protein in the neutrophils and monocytes of a patient with chronic idiopathic thrombocytopenic purpura or possible early myelodysplasia? 750 Jun 49

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

Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic stem cell disorder with myelodysplastic and myeloproliferative overlap features, and an inherent tendency to transform to acute myeloid leukaemia. Approximately 30% of patients present with clonal cytogenetic abnormalities, while almost 90% have molecular aberrations involving epigenetic regulation, the spliceosome component machinery, tumour suppressor genes and transcription factors/regulators. Numerous prognostic models exist for CMML, with more recent models incorporating prognostic mutations, such as those involving ASXL1. Other variables that seem to consistently affect outcomes include the degree of leucocytosis/monocytosis, anaemia and thrombocytopenia. Allogeneic stem cell transplant remains the only curative option for CMML, while hypomethylating agents can be used for transplant-ineligible patients or those without suitable stem cell sources. Targeting biological pathways activated in CMML offers potential hope for more effective and less toxic therapies.
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PMID:Chronic myelomonocytic leukaemia: a concise clinical and pathophysiological review. 2446 17