Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Leukemia ; 30(2): 431-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26449662

ABSTRACT

A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation of CALR, the calreticulin gene. A 52-bp deletion (type 1) and a 5-bp insertion (type 2 mutation) are the most frequent variants. These indels might differentially impair the calcium binding activity of mutant calreticulin. We studied the relationship between mutation subtype and biological/clinical features of the disease. Thirty-two different types of CALR variants were identified in 311 patients. Based on their predicted effect on calreticulin C-terminal, mutations were classified as: (i) type 1-like (65%); (ii) type 2-like (32%); and (iii) other types (3%). Corresponding CALR mutants had significantly different estimated isoelectric points. Patients with type 1 mutation, but not those with type 2, showed abnormal cytosolic calcium signals in cultured megakaryocytes. Type 1-like mutations were mainly associated with a myelofibrosis phenotype and a significantly higher risk of myelofibrotic transformation in essential thrombocythemia. Type 2-like CALR mutations were preferentially associated with an essential thrombocythemia phenotype, low risk of thrombosis despite very-high platelet counts and indolent clinical course. Thus, mutation subtype contributes to determining clinical phenotype and outcomes in CALR-mutant myeloproliferative neoplasms. CALR variants that markedly impair the calcium binding activity of mutant calreticulin are mainly associated with a myelofibrosis phenotype.


Subject(s)
Calreticulin/genetics , Mutation , Primary Myelofibrosis/genetics , Thrombocythemia, Essential/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Calcium/metabolism , Cells, Cultured , Exons , Female , Humans , Isoelectric Point , Male , Megakaryocytes/metabolism , Middle Aged , Primary Myelofibrosis/metabolism , Thrombocythemia, Essential/metabolism
2.
J Bacteriol ; 175(12): 3863-75, 1993 Jun.
Article in English | MEDLINE | ID: mdl-7685336

ABSTRACT

Acetoin is a major extracellular product of Bacillus subtilis grown on glucose and other fermentable carbon sources. The enzymes responsible for the formation of acetoin, acetolactate synthase, and acetolactate decarboxylase are synthesized in detectable amounts only in cells that have reached stationary phase. We have cloned and sequenced the genes encoding these enzymes, alsS and alsD, as well as a gene, alsR, that regulates their expression. alsS and alsD appear to compose a single operon, while alsR is transcribed divergently from the alsSD operon. AlsR shows significant homology to the LysR family of bacterial activator proteins, and when alsR is disrupted the alsSD operon is not expressed. Transcriptional fusions to alsS and alsR revealed that AlsR is required for the transcription of the alsSD operon, which increases during stationary phase. Two mutations that cause increased expression of the alsSD operon have been isolated, cloned, and sequenced. They each change an amino acid in the AlsR protein.


Subject(s)
Acetoin/metabolism , Acetolactate Synthase/genetics , Bacillus subtilis/genetics , Gene Expression Regulation, Bacterial , Genes, Bacterial , Alleles , Amino Acid Sequence , Base Sequence , Chromosome Mapping , Cloning, Molecular , Molecular Sequence Data , Mutagenesis, Insertional , Operon , Promoter Regions, Genetic , RNA, Bacterial/genetics , RNA, Messenger/genetics , Restriction Mapping , Transcription, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL
...