Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurofibromatosis 1 (NF1) gene product, neurofibromin, contains a GTPase-activating protein (GAP)-related domain, or NF1 GRD, that is able to down-regulate p21ras by stimulating its intrinsic GTPase. Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. We describe an amino acid substitution in the NF1 GRD, altering Lys-1423, that has occurred in three tumor types: colon adenocarcinoma, myelodysplastic syndrome, and anaplastic astrocytoma, and in one family with neurofibromatosis 1. The GAP activity of the mutant NF1 GRD is 200- to 400-fold lower than that of wild type, whereas binding affinity is unaffected. Thus, germline mutations in NF1 that cause neurofibromatosis 1 can also occur in somatic cells and contribute to the development of sporadic tumors, including tumors not associated with neurofibromatosis 1.
 ...
PMID:Somatic mutations in the neurofibromatosis 1 gene in human tumors. 156 47

Neurofibromatosis 1 gene (NF1) is a tumor suppressor gene and the product of which down-regulates Nras protein by its GTPase activating protein-related domain (NF1-GRD). Although the incidence of NF1 mutation was reported to be rare in the chronic phase of myelodysplastic syndrome (MDS), there have been no previous reports on its configuration in patients showing the disease progression. We examined NF1 in 50 patients with MDS including 9 who had progressed to more advanced stages and 16 to acute leukemia. Six patients had an Nras mutation. We carried out allele specific restriction analysis (ASRA) to detect a mutation at the first nucleotide A of codon 1423 (AAG), a mutational hot spot. We also employed a polymerase chain reaction mediated single strand conformation polymorphism (PCR-SSCP) method to confirm the result of ASRA and to detect a point mutation in other sequences of FLR exon. In consequence, ASRA disclosed wild type configuration and PCR-SSCP showed no aberrant band in any sample examined whether the samples harboured an Nras mutation or not. We conclude that NF1 mutation does not play a crucial role in the development and the progression of MDS.
 ...
PMID:Neurofibromatosis 1 gene (NF1) mutation is a rare genetic event in myelodysplastic syndrome regardless of the disease progression. 759 22

Hyperthyroidism can be associated with various haematological disorders related to several mechanisms. These disorders might be related to the reduced life-span of whole blood components and/or to an autoimmune mechanism. Only one case of pancytopenia has yet been reported. The observation of 3 new personal cases (1 toxic adenoma and 2 Graves' disease) led us to review the pathogeny of haematological disorders found in hyperthyroidism. Only one patient had antineutrophil autoantibodies. Direct and indirect Coomb's test, and Dixon's test were negative. In all patients, bone marrow aspiration was unable to demonstrate pernicious anaemia or myelodysplastic syndrome. Two patients presented cytological signs of macrophage activation with eosinophilia. These cytological features were compatible with an immuno-allergy mechanism. All haematological disorders disappeared when patients became euthyroid. In all cases, the haematological abnormalities were quite mild and might have gone unnoticed. Thus, it can be suggested that the frequency of pancytopenia in hyperthyroidism is underestimated.
 ...
PMID:[Pancytopenia resolved by the treatment of hyperthyroidism]. 763 Aug 70

Hematopoietic stem cell transplantation (HSCT) can either cause or eliminate autoimmune disease. Here, we report two cases. One was a 33-year-old woman with myelodysplastic syndrome (refractory anemia) who received bone marrow transplantation from her human leukocyte antigen (HLA)-identical sister who had a history of Graves disease. Antithyroid antibodies, including antimicrosomal antibody and antithyroglobulin antibody, appeared 4 months after transplantation. Clinical hyperthyroidism appeared 7 months after transplantation, and a hypothyroid state was noted 2 months later. The other case was a 50-year-old woman with Sjgrens syndrome and hypothyroidism who was diagnosed with peripheral T cell non-Hodgkins lymphoma. She received allogeneic peripheral blood stem cell transplantation (PBSCT) from her histocompatible sister owing to only partial response to traditional chemotherapy. Cure of lymphoma and remission of Sjgrens syndrome was noted 4 years after PBSCT. These two illustrative cases, one of acquisition of hyperthyroidism and the other of remission of Sjgrens syndrome after transplantation, highlights that HSCT can induce adoptive autoimmune disease or cure coincidental autoimmune disease. Donor selection and attentive monitoring is required in such circumstances.
 ...
PMID:Acquisition and cure of autoimmune disease following allogeneic hematopoietic stem cell transplantation. 1790 68

Thiazolidinediones (TZDs) are frequently used pharmacotherapeutics for type II diabetes mellitus, which exert their effect through peroxisomal proliferator agonist receptor (PPAR) mediated increased insulin sensitivity. TZDs are known to cause marrow suppression and to stimulate adipogenesis. Case and cohort studies show TZDs worsen thyroid-associated orbitopathy. We present a case consistent with earlier reports of marrow suppressive pancytopenia manifesting as myelodysplastic syndrome, a new implication of hypoerythropoetinemia, and non-Graves'-associated proliferative proptosis.
 ...
PMID:Marrow suppression with myelodysplastic features, hypoerythropoetinemia, and lipotrophic proptosis due to rosiglitazone. 2013 89